{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:17:56Z","timestamp":1792682276817,"version":"4.5.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,2,8]]},"abstract":"<jats:p>\n                    The large GTPase atlastin belongs to the dynamin superfamily that has been widely implicated in facilitating membrane tubulation, fission, and in select cases, fusion. Mutations spread across atlastin isoform 1 (atlastin-1) have been identified in patients suffering from hereditary spastic paraplegia (HSP), a neurodegenerative disorder affecting motor neuron function in the lower extremities. On a molecular level, atlastin-1 associates with high membrane curvature and fusion events at the endoplasmic reticulum and\n                    <jats:italic>cis<\/jats:italic>\n                    -Golgi. Here we report crystal structures of atlastin-1 comprising the G and middle domains in two different conformations. Although the orientation of the middle domain relative to the G domain is different in the two structures, both reveal dimeric assemblies with a common, GDP-bound G domain dimer. In contrast, dimer formation in solution is observed only in the presence of GTP and transition state analogs, similar to other G proteins that are activated by nucleotide-dependent dimerization. Analyses of solution scattering data suggest that upon nucleotide binding, the protein adopts a somewhat extended, dimeric conformation that is reminiscent of one of the two crystal structures. These structural studies suggest a model for nucleotide-dependent regulation of atlastin with implications for membrane fusion. This mechanism is affected in several mutants associated with HSP, providing insights into disease pathogenesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1012792108","type":"journal-article","created":{"date-parts":[[2011,1,10]],"date-time":"2011-01-10T23:55:41Z","timestamp":1294703741000},"page":"2216-2221","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":172,"title":["Structural basis for the nucleotide-dependent dimerization of the large G protein atlastin-1\/SPG3A"],"prefix":"10.1073","volume":"108","author":[{"given":"Laura J.","family":"Byrnes","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Sondermann","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,1,10]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrm1313","article-title":"The dynamin superfamily: universal membrane tubulation and fission molecules?","volume":"5","author":"Praefcke GJK","year":"2004","unstructured":"GJK Praefcke, HT McMahon, The dynamin superfamily: universal membrane tubulation and fission molecules? Nat Rev Mol Cell Biol 5, 133\u2013147 (2004).","journal-title":"Nat Rev Mol Cell Biol"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nrm2689","article-title":"It takes two to tango: Regulation of G proteins by dimerization","volume":"10","author":"Gasper R","year":"2009","unstructured":"R Gasper, S Meyer, K Gotthardt, M Sirajuddin, A Wittinghofer, It takes two to tango: Regulation of G proteins by dimerization. Nat Rev Mol Cell Biol 10, 423\u2013429 (2009).","journal-title":"Nat Rev Mol Cell Biol"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/35000617","article-title":"Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins","volume":"403","author":"Prakash B","year":"2000","unstructured":"B Prakash, GJ Praefcke, L Renault, A Wittinghofer, C Herrmann, Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins. Nature 403, 567\u2013571 (2000).","journal-title":"Nature"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nature09032","article-title":"G domain dimerization controls dynamin\u2019s assembly-stimulated GTPase activity","volume":"465","author":"Chappie JS","year":"2010","unstructured":"JS Chappie, S Acharya, M Leonard, SL Schmid, F Dyda, G domain dimerization controls dynamin\u2019s assembly-stimulated GTPase activity. Nature 465, 435\u2013440 (2010).","journal-title":"Nature"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1042\/BST0371022","article-title":"Dissecting dynamin\u2019s role in clathrin-mediated endocytosis","volume":"37","author":"Mettlen M","year":"2009","unstructured":"M Mettlen, T Pucadyil, R Ramachandran, SL Schmid, Dissecting dynamin\u2019s role in clathrin-mediated endocytosis. Biochem Soc Trans 37, 1022\u20131026 (2009).","journal-title":"Biochem Soc Trans"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1038\/ncb1001-922","article-title":"Three-dimensional reconstruction of dynamin in the constricted state","volume":"3","author":"Zhang P","year":"2001","unstructured":"P Zhang, JE Hinshaw, Three-dimensional reconstruction of dynamin in the constricted state. Nat Cell Biol 3, 922\u2013926 (2001).","journal-title":"Nat Cell Biol"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1038\/emboj.2010.187","article-title":"Dynamin GTPase regulation is altered by PH domain mutations found in centronuclear myopathy patients","volume":"29","author":"Kenniston JA","year":"2010","unstructured":"JA Kenniston, MA Lemmon, Dynamin GTPase regulation is altered by PH domain mutations found in centronuclear myopathy patients. EMBO J 29, 3054\u20133067 (2010).","journal-title":"EMBO J"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1091\/mbc.e09-04-0318","article-title":"An intramolecular signaling element that modulates dynamin function in vitro and in vivo","volume":"20","author":"Chappie JS","year":"2009","unstructured":"JS Chappie, et al., An intramolecular signaling element that modulates dynamin function in vitro and in vivo. Mol Biol Cell 20, 3561\u20133571 (2009).","journal-title":"Mol Biol Cell"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2008.11.028","article-title":"GTPase cycle of dynamin is coupled to membrane squeeze and release, leading to spontaneous fission","volume":"135","author":"Bashkirov PV","year":"2008","unstructured":"PV Bashkirov, et al., GTPase cycle of dynamin is coupled to membrane squeeze and release, leading to spontaneous fission. Cell 135, 1276\u20131286 (2008).","journal-title":"Cell"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"30842","DOI":"10.1016\/S0021-9258(18)47358-9","article-title":"Activation of dynamin GTPase is a result of positive cooperativity","volume":"269","author":"Tuma PL","year":"1994","unstructured":"PL Tuma, CA Collins, Activation of dynamin GTPase is a result of positive cooperativity. J Biol Chem 269, 30842\u201330847 (1994).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"22310","DOI":"10.1074\/jbc.271.37.22310","article-title":"Dynamin self-assembly stimulates its GTPase activity","volume":"271","author":"Warnock DE","year":"1996","unstructured":"DE Warnock, JE Hinshaw, SL Schmid, Dynamin self-assembly stimulates its GTPase activity. J Biol Chem 271, 22310\u201322314 (1996).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/nature08972","article-title":"Structural basis of oligomerization in the stalk region of dynamin-like MxA","volume":"465","author":"Gao S","year":"2010","unstructured":"S Gao, et al., Structural basis of oligomerization in the stalk region of dynamin-like MxA. Nature 465, 502\u2013506 (2010).","journal-title":"Nature"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/ng758","article-title":"Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia","volume":"29","author":"Zhao X","year":"2001","unstructured":"X Zhao, et al., Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia. Nat Genet 29, 326\u2013331 (2001).","journal-title":"Nat Genet"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.cell.2009.05.025","article-title":"A class of dynamin-like GTPases involved in the generation of the tubular ER network","volume":"138","author":"Hu J","year":"2009","unstructured":"J Hu, et al., A class of dynamin-like GTPases involved in the generation of the tubular ER network. Cell 138, 549\u2013561 (2009).","journal-title":"Cell"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1038\/nature08280","article-title":"Homotypic fusion of ER membranes requires the dynamin-like GTPase Atlastin","volume":"460","author":"Orso G","year":"2009","unstructured":"G Orso, et al., Homotypic fusion of ER membranes requires the dynamin-like GTPase Atlastin. Nature 460, 978\u2013983 (2009).","journal-title":"Nature"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mcn.2007.01.012","article-title":"Mutations in the SPG3A gene encoding the GTPase atlastin interfere with vesicle trafficking in the ER\/Golgi interface and Golgi morphogenesis","volume":"35","author":"Namekawa M","year":"2007","unstructured":"M Namekawa, et al., Mutations in the SPG3A gene encoding the GTPase atlastin interfere with vesicle trafficking in the ER\/Golgi interface and Golgi morphogenesis. Mol Cell Neurosci 35, 1\u201313 (2007).","journal-title":"Mol Cell Neurosci"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1111\/j.1471-4159.2009.06258.x","article-title":"Atlastin-1, the dynamin-like GTPase responsible for spastic paraplegia SPG3A, remodels lipid membranes and may form tubules and vesicles in the endoplasmic reticulum","volume":"110","author":"Muriel M","year":"2009","unstructured":"M Muriel, et al., Atlastin-1, the dynamin-like GTPase responsible for spastic paraplegia SPG3A, remodels lipid membranes and may form tubules and vesicles in the endoplasmic reticulum. J Neurochem 110, 1607\u20131616 (2009).","journal-title":"J Neurochem"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1093\/hmg\/ddn046","article-title":"Atlastin GTPases are required for Golgi apparatus and ER morphogenesis","volume":"17","author":"Rismanchi N","year":"2008","unstructured":"N Rismanchi, C Soderblom, J Stadler, P-P Zhu, C Blackstone, Atlastin GTPases are required for Golgi apparatus and ER morphogenesis. Hum Mol Genet 17, 1591\u20131604 (2008).","journal-title":"Hum Mol Genet"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"49063","DOI":"10.1074\/jbc.M306702200","article-title":"Cellular localization, oligomerization, and membrane association of the hereditary spastic paraplegia 3A (SPG3A) protein atlastin","volume":"278","author":"Zhu P-P","year":"2003","unstructured":"P-P Zhu, et al., Cellular localization, oligomerization, and membrane association of the hereditary spastic paraplegia 3A (SPG3A) protein atlastin. J Biol Chem 278, 49063\u201349071 (2003).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1172\/JCI40979","article-title":"Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network","volume":"120","author":"Park SH","year":"2010","unstructured":"SH Park, P-P Zhu, RL Parker, C Blackstone, Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network. J Clin Invest 120, 1097\u20131110 (2010).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"10666","DOI":"10.1073\/pnas.0510863103","article-title":"Interaction of two hereditary spastic paraplegia gene products, spastin and atlastin, suggests a common pathway for axonal maintenance","volume":"103","author":"Evans K","year":"2006","unstructured":"K Evans, et al., Interaction of two hereditary spastic paraplegia gene products, spastin and atlastin, suggests a common pathway for axonal maintenance. Proc Natl Acad Sci USA 103, 10666\u201310671 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/hmg\/ddi447","article-title":"Spastin and atlastin, two proteins mutated in autosomal-dominant hereditary spastic paraplegia, are binding partners","volume":"15","author":"Sanderson CM","year":"2006","unstructured":"CM Sanderson, et al., Spastin and atlastin, two proteins mutated in autosomal-dominant hereditary spastic paraplegia, are binding partners. Hum Mol Genet 15, 307\u2013318 (2006).","journal-title":"Hum Mol Genet"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s11910-996-0011-1","article-title":"Hereditary spastic paraplegia","volume":"6","author":"Fink JK","year":"2006","unstructured":"JK Fink, Hereditary spastic paraplegia. Curr Neurol Neurosci Rep 6, 65\u201376 (2006).","journal-title":"Curr Neurol Neurosci Rep"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/j.1399-0004.2009.01184.x","article-title":"Four novel SPG3A\/atlastin mutations identified in autosomal dominant hereditary spastic paraplegia kindreds with intra-familial variability in age of onset and complex phenotype","volume":"75","author":"Smith BN","year":"2009","unstructured":"BN Smith, et al., Four novel SPG3A\/atlastin mutations identified in autosomal dominant hereditary spastic paraplegia kindreds with intra-familial variability in age of onset and complex phenotype. Clin Genet 75, 485\u2013489 (2009).","journal-title":"Clin Genet"},{"key":"e_1_3_4_25_2","article-title":"Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia","author":"McCorquodale D","year":"2010","unstructured":"D McCorquodale, et al., Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia. Clin Genet, 10.1111\/j.1399-0004.2010.01501.x. (2010).","journal-title":"Clin Genet"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1093\/hmg\/ddl054","article-title":"SPG3A protein atlastin-1 is enriched in growth cones and promotes axon elongation during neuronal development","volume":"15","author":"Zhu P-P","year":"2006","unstructured":"P-P Zhu, C Soderblom, J-H Tao-Cheng, J Stadler, C Blackstone, SPG3A protein atlastin-1 is enriched in growth cones and promotes axon elongation during neuronal development. Hum Mol Genet 15, 1343\u20131353 (2006).","journal-title":"Hum Mol Genet"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature04510","article-title":"How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP","volume":"440","author":"Ghosh A","year":"2006","unstructured":"A Ghosh, GJK Praefcke, L Renault, A Wittinghofer, C Herrmann, How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP. Nature 440, 101\u2013104 (2006).","journal-title":"Nature"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/nature05312","article-title":"A bacterial dynamin-like protein","volume":"444","author":"Low HH","year":"2006","unstructured":"HH Low, J Lowe, A bacterial dynamin-like protein. Nature 444, 766\u2013769 (2006).","journal-title":"Nature"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1017\/S0033583507004635","article-title":"X-ray solution scattering (SAXS) combined with crystallography and computation: Defining accurate macromolecular structures, conformations and assemblies in solution","volume":"40","author":"Putnam CD","year":"2007","unstructured":"CD Putnam, M Hammel, GL Hura, JA Tainer, X-ray solution scattering (SAXS) combined with crystallography and computation: Defining accurate macromolecular structures, conformations and assemblies in solution. Q Rev Biophys 40, 191\u2013285 (2007).","journal-title":"Q Rev Biophys"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1017\/S0033583503003871","article-title":"Small-angle scattering: a view on the properties, structures and structural changes of biological macromolecules in solution","volume":"36","author":"Koch MH","year":"2003","unstructured":"MH Koch, P Vachette, DI Svergun, Small-angle scattering: a view on the properties, structures and structural changes of biological macromolecules in solution. Q Rev Biophys 36, 147\u2013227 (2003).","journal-title":"Q Rev Biophys"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1016\/S0006-3495(01)76260-1","article-title":"Determination of domain structure of proteins from X-ray solution scattering","volume":"80","author":"Svergun DI","year":"2001","unstructured":"DI Svergun, MV Petoukhov, MHJ Koch, Determination of domain structure of proteins from X-ray solution scattering. Biophys J 80, 2946\u20132953 (2001).","journal-title":"Biophys J"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jmb.2004.09.026","article-title":"Identification of residues in the human guanylate-binding protein 1 critical for nucleotide binding and cooperative GTP hydrolysis","volume":"344","author":"Praefcke GJK","year":"2004","unstructured":"GJK Praefcke, et al., Identification of residues in the human guanylate-binding protein 1 critical for nucleotide binding and cooperative GTP hydrolysis. J Mol Biol 344, 257\u2013269 (2004).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","DOI":"10.1126\/stke.2000.50.pe1","article-title":"Conformational display: A role for switch polymorphism in the superfamily of regulatory GTPases","volume":"2000","author":"Sprang SR","year":"2000","unstructured":"SR Sprang, Conformational display: A role for switch polymorphism in the superfamily of regulatory GTPases. Sci STKE 2000, pe1. (2000).","journal-title":"Sci STKE"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1017\/S0033583506004306","article-title":"Structural basis of function in heterotrimeric G proteins","volume":"39","author":"Oldham WM","year":"2006","unstructured":"WM Oldham, HE Hamm, Structural basis of function in heterotrimeric G proteins. Q Rev Biophys 39, 117\u2013166 (2006).","journal-title":"Q Rev Biophys"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","article-title":"Processing of X-ray diffraction data collected in oscillation mode","volume":"276","author":"Otwinowski Z","year":"1997","unstructured":"Z Otwinowski, W Minor, Processing of X-ray diffraction data collected in oscillation mode. Method Enzymol 276, 307\u2013326 (1997).","journal-title":"Method Enzymol"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1107\/S0907444902016657","article-title":"PHENIX: Building new software for automated crystallographic structure determination","volume":"58","author":"Adams PD","year":"2002","unstructured":"PD Adams, et al., PHENIX: Building new software for automated crystallographic structure determination. Acta Crystallogr D 58, 1948\u20131954 (2002).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: Model-building tools for molecular graphics","volume":"60","author":"Emsley P","year":"2004","unstructured":"P Emsley, K Cowtan, Coot: Model-building tools for molecular graphics. Acta Crystallogr D 60, 2126\u20132132 (2004).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","DOI":"10.1107\/S0021889807002853","article-title":"ATSAS 2.1\u2014Towards automated and web-supported small-angle scattering data analysis","volume":"40","author":"Petoukhov MV","year":"2007","unstructured":"MV Petoukhov, PV Konarev, AG Kikhney, DI Svergun, ATSAS 2.1\u2014Towards automated and web-supported small-angle scattering data analysis. J Appl Crystallogr 40\u2013228 (2007).","journal-title":"J Appl Crystallogr"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1012792108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T04:19:45Z","timestamp":1654575585000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1012792108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1,10]]},"references-count":38,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,2,8]]}},"alternative-id":["10.1073\/pnas.1012792108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1012792108","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.9029957.793495839","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.9029957.9591062","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.9029957.9833061","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.9029957.13512055","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1,10]]},"assertion":[{"value":"2011-01-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}