PMID- 23623730 OWN - NLM STAT- MEDLINE DCOM- 20140130 LR - 20130513 IS - 1878-4186 (Electronic) IS - 0969-2126 (Linking) VI - 21 IP - 5 DP - 2013 May 7 TI - An atomistic view of microtubule stabilization by GTP. PG - 833-43 LID - S0969-2126(13)00107-X [pii] LID - 10.1016/j.str.2013.03.009 [doi] AB - A microtubule is a dynamic system formed of alphabeta-tubulins. The presence of nonhydrolyzable guanosine-5'-triphosphate (GTP)/guanosine diphosphate (GDP) on the beta-tubulins provokes microtubule polymerization/depolymerization. Despite the large number of experimental studies of this dynamical process, its mechanism is still unclear. To provide insights into this mechanism we studied the first depolymerization steps of GDP/GTP-bound microtubules by normal-mode analysis with the all-atom model. We also constructed a depolymerizing microtubule and compared it to cryo-electron microscopy tomograms (cyro-ET). The results show that during depolymerization, the protofilaments not only curve but twist to weaken their lateral interactions. These interactions are stabilized by GTP, but not evenly. Not all of the interface residues are of equal importance: five of them, belonging to the H2-S3 loop, play a special role; acting as a lock whose key is the gamma-phosphate of GTP. Sequence alignments of several tubulins confirm the importance of these residues. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Quiniou, Eric AU - Quiniou E AD - Institut Curie, Centre de Recherche, U759, Bat. 112, Centre Universitaire, 91405 Orsay Cedex, France. FAU - Guichard, Paul AU - Guichard P FAU - Perahia, David AU - Perahia D FAU - Marco, Sergio AU - Marco S FAU - Mouawad, Liliane AU - Mouawad L LA - eng PT - Journal Article DEP - 20130425 PL - United States TA - Structure JT - Structure (London, England : 1993) JID - 101087697 RN - 0 (Tubulin) RN - 146-91-8 (Guanosine Diphosphate) RN - 86-01-1 (Guanosine Triphosphate) SB - IM MH - Cryoelectron Microscopy MH - Guanosine Diphosphate/chemistry/metabolism MH - Guanosine Triphosphate/chemistry/*metabolism MH - Kinetics MH - Microtubules/*chemistry/metabolism MH - Protein Conformation MH - Sequence Alignment MH - Tubulin/chemistry/metabolism EDAT- 2013/04/30 06:00 MHDA- 2014/01/31 06:00 CRDT- 2013/04/30 06:00 PHST- 2012/10/29 00:00 [received] PHST- 2013/02/08 00:00 [revised] PHST- 2013/03/08 00:00 [accepted] PHST- 2013/04/30 06:00 [entrez] PHST- 2013/04/30 06:00 [pubmed] PHST- 2014/01/31 06:00 [medline] AID - S0969-2126(13)00107-X [pii] AID - 10.1016/j.str.2013.03.009 [doi] PST - ppublish SO - Structure. 2013 May 7;21(5):833-43. doi: 10.1016/j.str.2013.03.009. Epub 2013 Apr 25.