title: An atomistic view of microtubule stabilization by GTP.
abstract: A microtubule is a dynamic system formed of αβ-tubulins. The presence of nonhydrolyzable guanosine-5'-triphosphate (GTP)/guanosine diphosphate (GDP) on the β-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 γ-phosphate of GTP. Sequence alignments of several tubulins confirm the importance of these residues.
authors.affiliation: Institut Curie, Centre de Recherche, U759, Bât. 112, Centre Universitaire, 91405 Orsay Cedex, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Quiniou
authors.forename: Paul
authors.initials: P
authors.lastname: Guichard
authors.forename: David
authors.initials: D
authors.lastname: Perahia
authors.forename: Sergio
authors.initials: S
authors.lastname: Marco
authors.forename: Liliane
authors.initials: L
authors.lastname: Mouawad
mesh_terms: D020285:Cryoelectron Microscopy; D006153:Guanosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D016415:Sequence Alignment; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D014404:Tubulin; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate