Structural rearrangements in tubulin following microtubule formation.
Microtubules are essential cytoskeletal structures that mediate several dynamic processes in a cell. To shed light on the structural processes relating to microtubule formation and dynamic instability, we investigated microtubules composed of 15 protofilaments using cryo-electron microscopy, helical image reconstruction and computational modelling. Analysis of the configuration of the alpha beta-tubulin heterodimer shows distinct structural differences in both subunits, and illustrates that the tubulin subunits have different roles in the microtubule lattice. Our modelling data suggest that after GTP hydrolysis microtubules, adopt a conformational state somewhere between a straight protofilament conformation--as found in zinc-induced tubulin sheets--and an outward curved conformation--as found in tubulin-stathmin complexes. The tendency towards a curved conformation seems to be mediated mostly by beta-tubulin, whereas alpha-tubulin resembles a state more related to the straight structure. Our data suggest a possible explanation of dynamic instability of microtubules, and for nucleotide-sensitive microtubule-binding properties of microtubule-associated proteins and molecular motors.
Krebs
Angelika
A
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. krebs@embl-heidelberg.de
Goldie
Kenneth N
KN
Hoenger
Andreas
A
D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D019281:Dimerization; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism*
D001704:Biopolymers; D014404:Tubulin
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