3jas | pdb_00003jas
Cryo-EM structure of dynamic GDP-microtubule (14 protofilaments) decorated with kinesin
Structural highlights
Function[TBA1B_PIG] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. [TBB_PIG] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. Publication Abstract from PubMedMicrotubule (MT) dynamic instability is driven by GTP hydrolysis and regulated by microtubule-associated proteins, including the plus-end tracking end-binding protein (EB) family. We report six cryo-electron microscopy (cryo-EM) structures of MTs, at 3.5 A or better resolution, bound to GMPCPP, GTPgammaS, or GDP, either decorated with kinesin motor domain after polymerization or copolymerized with EB3. Subtle changes around the E-site nucleotide during hydrolysis trigger conformational changes in alpha-tubulin around an "anchor point," leading to global lattice rearrangements and strain generation. Unlike the extended lattice of the GMPCPP-MT, the EB3-bound GTPgammaS-MT has a compacted lattice that differs in lattice twist from that of the also compacted GDP-MT. These results and the observation that EB3 promotes rapid hydrolysis of GMPCPP suggest that EB proteins modulate structural transitions at growing MT ends by recognizing and promoting an intermediate state generated during GTP hydrolysis. Our findings explain both EBs end-tracking behavior and their effect on microtubule dynamics. Mechanistic Origin of Microtubule Dynamic Instability and Its Modulation by EB Proteins.,Zhang R, Alushin GM, Brown A, Nogales E Cell. 2015 Jul 28. pii: S0092-8674(15)00849-1. doi: 10.1016/j.cell.2015.07.012. PMID:26234155[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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