An Atomistic View of Microtubule Stabilization by GTP
Résumé
A microtubule is a dynamic system formed of
ab-tubulins. The presence of nonhydrolyzable
guanosine-50-triphosphate (GTP)/guanosine diphosphate
(GDP) on the b-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 mechanismwe 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 g-phosphate
of GTP. Sequence alignments of several tubulins
confirm the importance of these residues.