{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:24:32Z","timestamp":1792009472789,"version":"4.4.0"},"reference-count":83,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["24302881"],"award-info":[{"award-number":["24302881"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:p>\n                    Charcot\u2013Marie\u2013Tooth disease (CMT) is the most common inherited peripheral polyneuropathy in humans, and its different subtypes are linked to mutations in dozens of different genes. Mutations in ganglioside\u2010induced differentiation\u2010associated protein 1 (GDAP1) cause two types of CMT, demyelinating CMT4A and axonal CMT2K. The GDAP1\u2010linked CMT genotypes are mainly missense point mutations. Despite clinical profiling and\n                    <jats:italic>in\u2009vivo<\/jats:italic>\n                    studies on the mutations, the etiology of GDAP1\u2010linked CMT is poorly understood. Here, we describe the biochemical and structural properties of the Finnish founding CMT2K mutation H123R and CMT2K\u2010linked R120W, both of which are autosomal dominant mutations. The disease variant proteins retain close to normal structure and solution behavior, but both present a significant decrease in thermal stability. Using GDAP1 variant crystal structures, we identify a side\u2010chain interaction network between helices \u237a3, \u237a6, and \u237a7, which is affected by CMT mutations, as well as a hinge in the long helix \u237a6, which is linked to structural flexibility. Structural analysis of GDAP1 indicates that CMT may arise from disruption of specific intra\u2010 and intermolecular interaction networks, leading to alterations in GDAP1 structure and stability, and, eventually, insufficient motor and sensory neuron function.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.13422","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:37:31Z","timestamp":1651711051000},"page":"1306-1324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Structural insights into Charcot\u2013Marie\u2013Tooth disease\u2010linked mutations in human GDAP1"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6704-1702","authenticated-orcid":false,"given":"Aleksi","family":"Sutinen","sequence":"first","affiliation":[{"name":"Faculty of Biochemistry and Molecular Medicine &amp; Biocenter Oulu University of Oulu  Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3536-9903","authenticated-orcid":false,"given":"Giang Thi Tuyet","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry and Molecular Medicine &amp; Biocenter Oulu University of Oulu  Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9443-9959","authenticated-orcid":false,"given":"Arne","family":"Raasakka","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen  Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6642-3909","authenticated-orcid":false,"given":"Gopinath","family":"Muruganandam","sequence":"additional","affiliation":[{"name":"VIB\u2010VUB Center for Structural Biology Vlaams Instituut voor Biotechnologie  Brussels Belgium"},{"name":"Structural Biology Brussels Department of Bioengineering Sciences Vrije Universiteit Brussel  Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remy","family":"Loris","sequence":"additional","affiliation":[{"name":"VIB\u2010VUB Center for Structural Biology Vlaams Instituut voor Biotechnologie  Brussels Belgium"},{"name":"Structural Biology Brussels Department of Bioengineering Sciences Vrije Universiteit Brussel  Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"Ylikallio","sequence":"additional","affiliation":[{"name":"Stem Cells and Metabolism Research Program Faculty of Medicine University of Helsinki  Finland"},{"name":"Clinical Neurosciences, Neurology Helsinki University Hospital  Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henna","family":"Tyynismaa","sequence":"additional","affiliation":[{"name":"Stem Cells and Metabolism Research Program Faculty of Medicine University of Helsinki  Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-4648","authenticated-orcid":false,"given":"Luca","family":"Bartesaghi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Karolinska Institutet  Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9740-9077","authenticated-orcid":false,"given":"Salla","family":"Ruskamo","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry and Molecular Medicine &amp; Biocenter Oulu University of Oulu  Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8529-3751","authenticated-orcid":false,"given":"Petri","family":"Kursula","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry and Molecular Medicine &amp; Biocenter Oulu University of Oulu  Finland"},{"name":"Department of Biomedicine University of Bergen  Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19123807"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000373"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.106"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.31"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2010.09.006"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7132494"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318228fc70"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng796"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng798"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.21307\/ane-2018-002"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/0972-2327.53075"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-013-0358-9"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000629"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2010.00286.x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.035600"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200507087"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000110R"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.631232"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41389-017-0025-3"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.21.7202"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fob.2014.11.006"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.20121"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa243"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.03.010"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020914"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2021.105300"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1159\/000478860"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-2697(03)00286-0"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606179103"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2004.05.012"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1088-1204"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2005.01.016"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1140\/epjp\/i2016-16056-0"},{"key":"e_1_2_11_35_1","doi-asserted-by":"crossref","unstructured":"MeentsA ReimeB StuebeN FischerP WarmerM GoeriesD RoeverJ MeyerJ FischerJ BurkhardtA VartiainenI KarvinenP DavidC.Development of an in\u2010vacuum x\u2010ray microscope with cryogenic sample cooling for beamline P11 at PETRA III. 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