{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:31:23Z","timestamp":1792647083631,"version":"4.5.0"},"reference-count":94,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["P300PA_174358"],"award-info":[{"award-number":["P300PA_174358"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM071940"],"award-info":[{"award-number":["R01GM071940"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10RR23057"],"award-info":[{"award-number":["S10RR23057"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMR-1548924"],"award-info":[{"award-number":["DMR-1548924"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI052348"],"award-info":[{"award-number":["AI052348"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["P2BEP3_162094"],"award-info":[{"award-number":["P2BEP3_162094"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD018111"],"award-info":[{"award-number":["S10OD018111"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U24GM116792"],"award-info":[{"award-number":["U24GM116792"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI-1338135"],"award-info":[{"award-number":["DBI-1338135"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The 96-nm axonemal repeat includes dynein motors and accessory structures as the foundation for motility of eukaryotic flagella and cilia. However, high-resolution 3D axoneme structures are unavailable for organisms among the Excavates, which include pathogens of medical and economic importance. Here we report cryo electron tomography structures of the 96-nm repeat from Trypanosoma brucei, a protozoan parasite in the Excavate lineage that causes African trypanosomiasis. We examined bloodstream and procyclic life cycle stages, and a knockdown lacking DRC11\/CMF22 of the nexin dynein regulatory complex (NDRC). Sub-tomogram averaging yields a resolution of 21.8 \u00c5 for the 96-nm repeat. We discovered several lineage-specific structures, including novel inter-doublet linkages and microtubule inner proteins (MIPs). We establish that DRC11\/CMF22 is required for the NDRC proximal lobe that binds the adjacent doublet microtubule. We propose that lineage-specific elaboration of axoneme structure in T. brucei reflects adaptations to support unique motility needs in diverse host environments.<\/jats:p>","DOI":"10.7554\/elife.52058","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T08:00:25Z","timestamp":1573459225000},"source":"Crossref","is-referenced-by-count":70,"title":["Cryo electron tomography with volta phase plate reveals novel structural foundations of the 96-nm axonemal repeat in the pathogen Trypanosoma brucei"],"prefix":"10.7554","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7514-6811","authenticated-orcid":true,"given":"Simon","family":"Imhof","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3602-1199","authenticated-orcid":true,"given":"Jiayan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States"},{"name":"Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States"},{"name":"California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9922-7170","authenticated-orcid":true,"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States"},{"name":"California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States"},{"name":"Department of Bioengineering, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-9889","authenticated-orcid":true,"given":"Khanh Huy","family":"Bui","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, McGill University, Montreal, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoangkim","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Atanasov","sequence":"additional","affiliation":[{"name":"California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wong H","family":"Hui","sequence":"additional","affiliation":[{"name":"California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun Kai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, McGill University, Montreal, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8373-4717","authenticated-orcid":true,"given":"Z Hong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States"},{"name":"Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States"},{"name":"California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States"},{"name":"Department of Bioengineering, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6529-1273","authenticated-orcid":true,"given":"Kent L","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States"},{"name":"Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States"},{"name":"California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2019,11,11]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/jeu.12691","article-title":"Revisions to the classification, nomenclature, and diversity of eukaryotes","volume":"66","author":"Adl","year":"2019","journal-title":"The Journal of Eukaryotic Microbiology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1111\/j.1550-7408.1965.tb03247.x","article-title":"Ultrastructure of Trypanosoma lewisi: flagellum, microtubules, and the kinetoplast","volume":"12","author":"Anderson","year":"1965","journal-title":"The Journal of Protozoology"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/s41581-019-0116-9","article-title":"Cellular signalling by primary cilia in development, organ function and disease","volume":"15","author":"Anvarian","year":"2019","journal-title":"Nature Reviews Nephrology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"2788","DOI":"10.1091\/mbc.E15-01-0018","article-title":"DRC3 connects the N-DRC to dynein g to regulate flagellar waveform","volume":"26","author":"Awata","year":"2015","journal-title":"Molecular Biology of the Cell"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005448","article-title":"Species-Specific adaptations of trypanosome morphology and motility to the mammalian host","volume":"12","author":"Bargul","year":"2016","journal-title":"PLOS Pathogens"},{"key":"bib6","doi-asserted-by":"publisher","DOI":"10.1038\/35300","article-title":"Paraflagellar rod is vital for trypanosome motility","volume":"391","author":"Bastin","year":"1998","journal-title":"Nature"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1091\/mbc.e12-11-0801","article-title":"The N-DRC forms a conserved biochemical complex that maintains outer doublet alignment and limits microtubule sliding in motile axonemes","volume":"24","author":"Bower","year":"2013","journal-title":"Molecular Biology of the Cell"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1091\/mbc.E17-08-0510","article-title":"DRC2\/CCDC65 is a central hub for assembly of the nexin-dynein regulatory complex and other regulators of ciliary and flagellar motility","volume":"29","author":"Bower","year":"2018","journal-title":"Molecular Biology of the Cell"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/nature04541","article-title":"Flagellar motility is required for the viability of the bloodstream trypanosome","volume":"440","author":"Broadhead","year":"2006","journal-title":"Nature"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1083\/jcb.200903082","article-title":"Asymmetry of inner dynein arms and inter-doublet links in Chlamydomonas flagella","volume":"186","author":"Bui","year":"2009","journal-title":"The Journal of Cell Biology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1083\/jcb.201201120","article-title":"Polarity and asymmetry in the arrangement of dynein and related structures in the Chlamydomonas axoneme","volume":"198","author":"Bui","year":"2012","journal-title":"The Journal of Cell Biology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/nature01377","article-title":"Dynein structure and power stroke","volume":"421","author":"Burgess","year":"2003","journal-title":"Nature"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/0248-4900(88)90056-1","article-title":"The paraflagellar rod: a structure in search of a function","volume":"63","author":"Cachon","year":"1988","journal-title":"Biology of the Cell"},{"key":"bib14","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.17716","article-title":"The skin is a significant but overlooked anatomical reservoir for vector-borne african trypanosomes","volume":"5","author":"Capewell","year":"2016","journal-title":"eLife"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"3667","DOI":"10.1074\/jbc.274.6.3667","article-title":"Kinesin takes one 8-nm step for each ATP that it hydrolyzes","volume":"274","author":"Coy","year":"1999","journal-title":"Journal of Biological Chemistry"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ceb.2018.06.001","article-title":"Evolutionary origins and specialisation of membrane transport","volume":"53","author":"Dacks","year":"2018","journal-title":"Current Opinion in Cell Biology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.ceb.2012.11.005","article-title":"Alternative cytoskeletal landscapes: cytoskeletal novelty and evolution in basal excavate protists","volume":"25","author":"Dawson","year":"2013","journal-title":"Current Opinion in Cell Biology"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1016\/j.str.2017.08.008","article-title":"Near-Atomic resolution structure determination in Over-Focus with volta phase plate by Cs-Corrected Cryo-EM","volume":"25","author":"Fan","year":"2017","journal-title":"Structure"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jsb.2015.03.004","article-title":"Electron cryotomography of vitrified cells with a volta phase plate","volume":"190","author":"Fukuda","year":"2015","journal-title":"Journal of Structural Biology"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.cell.2009.03.023","article-title":"The vertebrate primary cilium in development, homeostasis, and disease","volume":"137","author":"Gerdes","year":"2009","journal-title":"Cell"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1126\/science.149.3682.424","article-title":"Dynein: a protein with adenosine triphosphatase activity from cilia","volume":"149","author":"Gibbons","year":"1965","journal-title":"Science"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1002\/pro.3235","article-title":"UCSF ChimeraX: meeting modern challenges in visualization and analysis","volume":"27","author":"Goddard","year":"2018","journal-title":"Protein Science"},{"key":"bib23","first-page":"1134","article-title":"Recherches et observations sur une nouvelle esp\u00e8ce d'h\u00e9matozoaire, Trypanosoma sanguinis","volume":"17","author":"Gruby","year":"1843","journal-title":"Comptes Rendus Hebdomadaire Des S\u00e9ances De l'Acad\u00e9mie Des Sciences, Paris"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"3859","DOI":"10.1073\/pnas.0807880106","article-title":"Phylogenomic analyses support the monophyly of excavata and resolve relationships among eukaryotic \"supergroups\"","volume":"106","author":"Hampl","year":"2009","journal-title":"PNAS"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003023","article-title":"Trypanosome motion represents an adaptation to the crowded environment of the vertebrate bloodstream","volume":"8","author":"Heddergott","year":"2012","journal-title":"PLOS Pathogens"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.jsb.2011.05.011","article-title":"Clustering and variance maps for cryo-electron tomography using wedge-masked differences","volume":"175","author":"Heumann","year":"2011","journal-title":"Journal of Structural Biology"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1083\/jcb.200908067","article-title":"The dynein regulatory complex is the nexin link and a major regulatory node in cilia and flagella","volume":"187","author":"Heuser","year":"2009","journal-title":"The Journal of Cell Biology"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"E2067","DOI":"10.1073\/pnas.1120690109","article-title":"Cryoelectron tomography reveals doublet-specific structures and unique interactions in the I1 dynein","volume":"109","author":"Heuser","year":"2012","journal-title":"PNAS"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"3143","DOI":"10.1091\/mbc.e12-05-0357","article-title":"The CSC connects three major axonemal complexes involved in dynein regulation","volume":"23","author":"Heuser","year":"2012","journal-title":"Molecular Biology of the Cell"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1128\/EC.2.2.200-208.2003","article-title":"Biology and mechanism of trypanosome cell motility","volume":"2","author":"Hill","year":"2003","journal-title":"Eukaryotic Cell"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/S0006-3495(90)82435-8","article-title":"A physical model of microtubule sliding in ciliary axonemes","volume":"58","author":"Holwill","year":"1990","journal-title":"Biophysical Journal"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/0092-8674(82)90381-6","article-title":"Suppressor mutations in Chlamydomonas reveal a regulatory mechanism for flagellar function","volume":"28","author":"Huang","year":"1982","journal-title":"Cell"},{"key":"bib33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025700","article-title":"Three-dimensional structure of the trypanosome flagellum suggests that the paraflagellar rod functions as a biomechanical spring","volume":"7","author":"Hughes","year":"2012","journal-title":"PLOS ONE"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/hmg\/ddg061","article-title":"To beat or not to beat: roles of cilia in development and disease","volume":"12","author":"Ibanez-Tallon","year":"2003","journal-title":"Human Molecular Genetics"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15035","article-title":"Subnanometre-resolution structure of the doublet microtubule reveals new classes of microtubule-associated proteins","volume":"8","author":"Ichikawa","year":"2017","journal-title":"Nature Communications"},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201700209","article-title":"Microtubule inner proteins: a meshwork of luminal proteins stabilizing the doublet microtubule","volume":"40","author":"Ichikawa","year":"2018","journal-title":"BioEssays"},{"key":"bib37","first-page":"393","volume-title":"Infectious Blood Diseases of Man and Animals","volume":"1","author":"Jahn","year":"1968"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1038\/s41556-018-0213-1","article-title":"The cryo-EM structure of intraflagellar transport trains reveals how dynein is inactivated to ensure unidirectional anterograde movement in cilia","volume":"20","author":"Jordan","year":"2018","journal-title":"Nature Cell Biology"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"3587","DOI":"10.1242\/jcs.073817","article-title":"CMF70 is a subunit of the dynein regulatory complex","volume":"123","author":"Kabututu","year":"2010","journal-title":"Journal of Cell Science"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"R278","DOI":"10.1016\/j.cub.2018.01.085","article-title":"Assembly, functions and evolution of archaella, flagella and cilia","volume":"28","author":"Khan","year":"2018","journal-title":"Current Biology"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1083\/jcb.201304099","article-title":"Big steps toward understanding dynein","volume":"202","author":"Kikkawa","year":"2013","journal-title":"The Journal of Cell Biology"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1002\/cm.21483","article-title":"Turning dyneins off bends cilia","volume":"75","author":"King","year":"2018","journal-title":"Cytoskeleton"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1111\/cmi.12244","article-title":"Mouse infection and pathogenesis by Trypanosoma brucei motility mutants","volume":"16","author":"Kisalu","year":"2014","journal-title":"Cellular Microbiology"},{"key":"bib44","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-5-209","article-title":"The origin and early evolution of eukaryotes in the light of phylogenomics","volume":"11","author":"Koonin","year":"2010","journal-title":"Genome Biology"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"11105","DOI":"10.1073\/pnas.1103634108","article-title":"Structure of Trypanosoma brucei flagellum accounts for its bihelical motion","volume":"108","author":"Koyfman","year":"2011","journal-title":"PNAS"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1006\/jsbi.1996.0013","article-title":"Computer visualization of three-dimensional image data using IMOD","volume":"116","author":"Kremer","year":"1996","journal-title":"Journal of Structural Biology"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/nmeth.2727","article-title":"Quantifying the local resolution of cryo-EM density maps","volume":"11","author":"Kucukelbir","year":"2014","journal-title":"Nature Methods"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/nrmicro3274","article-title":"Motility and more: the flagellum of Trypanosoma brucei","volume":"12","author":"Langousis","year":"2014","journal-title":"Nature Reviews Microbiology"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/nmeth.2472","article-title":"Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM","volume":"10","author":"Li","year":"2013","journal-title":"Nature Methods"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"29175","DOI":"10.1074\/jbc.M111.241760","article-title":"Building blocks of the nexin-dynein regulatory complex in Chlamydomonas flagella","volume":"286","author":"Lin","year":"2011","journal-title":"The Journal of Biological Chemistry"},{"key":"bib51","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6727","article-title":"Cryo-electron tomography reveals ciliary defects underlying human RSPH1 primary ciliary dyskinesia","volume":"5","author":"Lin","year":"2014","journal-title":"Nature Communications"},{"key":"bib52","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar1968","article-title":"Asymmetric distribution and spatial switching of dynein activity generates ciliary motility","volume":"360","author":"Lin","year":"2018","journal-title":"Science"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.jsb.2005.07.007","article-title":"Automated electron microscope tomography using robust prediction of specimen movements","volume":"152","author":"Mastronarde","year":"2005","journal-title":"Journal of Structural Biology"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/S1047-8477(03)00069-8","article-title":"Accurate determination of local defocus and specimen tilt in electron microscopy","volume":"142","author":"Mindell","year":"2003","journal-title":"Journal of Structural Biology"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1128\/EC.00068-13","article-title":"CMF22 is a broadly conserved axonemal protein and is required for propulsive motility in Trypanosoma brucei","volume":"12","author":"Nguyen","year":"2013","journal-title":"Eukaryotic Cell"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1126\/science.1128618","article-title":"The molecular architecture of axonemes revealed by cryoelectron tomography","volume":"313","author":"Nicastro","year":"2006","journal-title":"Science"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"E845","DOI":"10.1073\/pnas.1106178108","article-title":"Cryo-electron tomography reveals conserved features of doublet microtubules in flagella","volume":"108","author":"Nicastro","year":"2011","journal-title":"PNAS"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1126\/science.1260214","article-title":"A molecular ruler determines the repeat length in eukaryotic cilia and flagella","volume":"346","author":"Oda","year":"2014","journal-title":"Science"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1091\/mbc.E14-09-1367","article-title":"Detailed structural and biochemical characterization of the nexin-dynein regulatory complex","volume":"26","author":"Oda","year":"2014","journal-title":"Molecular Biology of the Cell"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1016\/j.ajhg.2015.08.012","article-title":"Loss-of-Function GAS8 mutations cause primary ciliary dyskinesia and disrupt the Nexin-Dynein regulatory complex","volume":"97","author":"Olbrich","year":"2015","journal-title":"The American Journal of Human Genetics"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09051-x","article-title":"Inner lumen proteins stabilize doublet microtubules in cilia and flagella","volume":"10","author":"Owa","year":"2019","journal-title":"Nature Communications"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF chimera--a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"Journal of Computational Chemistry"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.jsb.2012.02.012","article-title":"Comparative structural analysis of eukaryotic flagella and cilia from Chlamydomonas, tetrahymena, and sea urchins","volume":"178","author":"Pigino","year":"2012","journal-title":"Journal of Structural Biology"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"F37","DOI":"10.1083\/jcb.151.5.F37","article-title":"The 9 + 2 axoneme anchors multiple inner arm dyneins and a network of kinases and phosphatases that control motility","volume":"151","author":"Porter","year":"2000","journal-title":"The Journal of Cell Biology"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1128\/EC.5.4.696-711.2006","article-title":"Flagellar motility contributes to cytokinesis in Trypanosoma brucei and is modulated by an evolutionarily conserved dynein regulatory system","volume":"5","author":"Ralston","year":"2006","journal-title":"Eukaryotic Cell"},{"key":"bib66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020101","article-title":"Trypanin, a component of the flagellar Dynein regulatory complex, is essential in bloodstream form African trypanosomes","volume":"2","author":"Ralston","year":"2006","journal-title":"PLOS Pathogens"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/j.ijpara.2008.03.003","article-title":"The flagellum of Trypanosoma brucei: new tricks from an old dog","volume":"38","author":"Ralston","year":"2008","journal-title":"International Journal for Parasitology"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.cell.2006.05.046","article-title":"Single-molecule analysis of dynein processivity and stepping behavior","volume":"126","author":"Reck-Peterson","year":"2006","journal-title":"Cell"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"19322","DOI":"10.1073\/pnas.0907001106","article-title":"Propulsion of african trypanosomes is driven by bihelical waves with alternating chirality separated by kinks","volume":"106","author":"Rodr\u00edguez","year":"2009","journal-title":"PNAS"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1111\/cmi.12230","article-title":"Forward motility is essential for trypanosome infection in the tsetse fly","volume":"16","author":"Rotureau","year":"2014","journal-title":"Cellular Microbiology"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1128\/EC.00019-14","article-title":"Insect stage-specific receptor adenylate cyclases are localized to distinct subdomains of the Trypanosoma brucei flagellar membrane","volume":"13","author":"Saada","year":"2014","journal-title":"Eukaryotic Cell"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/S0166-6851(97)00149-7","article-title":"A motility function for the paraflagellar rod of leishmania parasites revealed by PFR-2 gene knockouts","volume":"90","author":"Santrich","year":"1997","journal-title":"Molecular and Biochemical Parasitology"},{"key":"bib73","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.39.1.77","article-title":"Studies on cilia","volume":"39","author":"Satir","year":"1968","journal-title":"The Journal of Cell Biology"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1093\/biosci\/biu180","article-title":"A structural basis for how motile cilia beat","volume":"64","author":"Satir","year":"2014","journal-title":"BioScience"},{"key":"bib75","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.27656","article-title":"Developmental adaptations of trypanosome motility to the tsetse fly host environments unravel a multifaceted in vivo microswimmer system","volume":"6","author":"Schuster","year":"2017","journal-title":"eLife"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1074\/mcp.M114.045146","article-title":"Cell surface proteomics provides insight into Stage-Specific remodeling of the Host-Parasite interface in Trypanosoma brucei","volume":"14","author":"Shimogawa","year":"2015","journal-title":"Molecular & Cellular Proteomics"},{"key":"bib77","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27228-0","article-title":"Parasite motility is critical for virulence of african trypanosomes","volume":"8","author":"Shimogawa","year":"2018","journal-title":"Scientific Reports"},{"key":"bib78","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007452","article-title":"Different functional states of fusion protein gB revealed on human Cytomegalovirus by cryo electron tomography with volta phase plate","volume":"14","author":"Si","year":"2018","journal-title":"PLOS Pathogens"},{"key":"bib79","article-title":"Cilia 2010: the surprise organelle of the decade","volume":"4","author":"Smith","year":"2010","journal-title":"Science Signaling"},{"key":"bib80","doi-asserted-by":"publisher","first-page":"5341","DOI":"10.1074\/jbc.M114.626556","article-title":"In situ localization of N and C termini of subunits of the flagellar nexin-dynein regulatory complex (N-DRC) using SNAP tag and cryo-electron tomography","volume":"290","author":"Song","year":"2015","journal-title":"Journal of Biological Chemistry"},{"key":"bib81","doi-asserted-by":"publisher","DOI":"10.1101\/363317","article-title":"Structure of the ciliary axoneme at nanometer resolution reconstructed by TYGRESS","volume-title":"bioRxiv","author":"Song","year":"2018"},{"key":"bib82","doi-asserted-by":"publisher","first-page":"2566","DOI":"10.1091\/mbc.E18-06-0405","article-title":"Tetrahymena RIB72A and RIB72B are microtubule inner proteins in the ciliary doublet microtubules","volume":"29","author":"Stoddard","year":"2018","journal-title":"Molecular Biology of the Cell"},{"key":"bib83","doi-asserted-by":"publisher","first-page":"E5916","DOI":"10.1073\/pnas.1722618115","article-title":"Flagellum couples cell shape to motility in Trypanosoma brucei","volume":"115","author":"Sun","year":"2018","journal-title":"PNAS"},{"key":"bib84","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.chom.2016.05.002","article-title":"Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice","volume":"19","author":"Trindade","year":"2016","journal-title":"Cell Host & Microbe"},{"key":"bib85","doi-asserted-by":"publisher","first-page":"R449","DOI":"10.1016\/j.cub.2006.05.041","article-title":"A post-assembly structural modification to the lumen of flagellar microtubule doublets","volume":"16","author":"Vaughan","year":"2006","journal-title":"Current Biology"},{"key":"bib86","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1242\/jcs.5.1.163","article-title":"On the surface coat and flagellar adhesion in trypanosomes","volume":"5","author":"Vickerman","year":"1969","journal-title":"Journal of Cell Science"},{"key":"bib87","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a018325","article-title":"Ciliary motility: regulation of axonemal dynein motors","volume":"9","author":"Viswanadha","year":"2017","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"bib88","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1038\/1891017a0","article-title":"Organization of function in trypanosome flagella","volume":"189","author":"Walker","year":"1961","journal-title":"Nature"},{"key":"bib89","article-title":"Movement of trypanosome flagella","volume":"10","author":"Walker","year":"1963","journal-title":"Journal of Protozoology"},{"key":"bib90","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/ng.2533","article-title":"The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans","volume":"45","author":"Wirschell","year":"2013","journal-title":"Nature Genetics"},{"key":"bib91","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/S0166-6851(99)00002-X","article-title":"A tightly regulated inducible expression system for conditional gene knock-outs and dominant-negative genetics in Trypanosoma brucei","volume":"99","author":"Wirtz","year":"1999","journal-title":"Molecular and Biochemical Parasitology"},{"key":"bib92","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.jsb.2009.08.016","article-title":"CTF determination and correction for low dose tomographic tilt series","volume":"168","author":"Xiong","year":"2009","journal-title":"Journal of Structural Biology"},{"key":"bib93","doi-asserted-by":"publisher","first-page":"41412","DOI":"10.1074\/jbc.M509072200","article-title":"An axonemal dynein particularly important for flagellar movement at high viscosity. Implications from a new Chlamydomonas mutant deficient in the dynein heavy chain gene DHC9","volume":"280","author":"Yagi","year":"2005","journal-title":"The Journal of Biological Chemistry"},{"key":"bib94","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1083\/jcb.201211048","article-title":"The MIA complex is a conserved and novel dynein regulator essential for normal ciliary motility","volume":"201","author":"Yamamoto","year":"2013","journal-title":"The Journal of Cell Biology"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/52058\/elife-52058-v3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/52058\/elife-52058-v3.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/52058","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:04:45Z","timestamp":1697058285000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/52058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,11]]},"references-count":94,"alternative-id":["10.7554\/eLife.52058"],"URL":"https:\/\/doi.org\/10.7554\/elife.52058","archive":["CLOCKSS"],"relation":{"is-supplemented-by":[{"id-type":"accession","id":"EMD-20014","asserted-by":"subject"},{"id-type":"accession","id":"EMD-20012","asserted-by":"subject"},{"id-type":"accession","id":"EMD-20013","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.52058.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.52058.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,11]]},"article-number":"e52058"}}