6vpp | pdb_00006vpp

Cryo-EM structure of microtubule-bound KLP61F motor with tail domain in the nucleotide-free state

Loading... Status: waiting for Mol* initialization Structural highlights 6vpp is a 3 chain structure with sequence from [1] and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GDP, GTP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TBA1A_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. [KL61_DROME] Important role in mitotic dividing cells. Microtubule motor required for spindle body separation. Slow plus-end directed microtubule motor capable of cross-linking and sliding apart antiparallel microtubules, thereby pushing apart the associated spindle poles during spindle assembly and function. [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 PubMed Kinesin-5 motors organize mitotic spindles by sliding apart microtubules. They are homotetramers with dimeric motor and tail domains at both ends of a bipolar minifilament. Here, we describe a regulatory mechanism involving direct binding between tail and motor domains and its fundamental role in microtubule sliding. Kinesin-5 tails decrease microtubule-stimulated ATP-hydrolysis by specifically engaging motor domains in the nucleotide-free or ADP states. Cryo-EM reveals that tail binding stabilizes an open motor domain ATP-active site. Full-length motors undergo slow motility and cluster together along microtubules, while tail-deleted motors exhibit rapid motility without clustering. The tail is critical for motors to zipper together two microtubules by generating substantial sliding forces. The tail is essential for mitotic spindle localization, which becomes severely reduced in tail-deleted motors. Our studies suggest a revised microtubule-sliding model, in which kinesin-5 tails stabilize motor domains in the microtubule-bound state by slowing ATP-binding, resulting in high-force production at both homotetramer ends. The kinesin-5 tail domain directly modulates the mechanochemical cycle of the motor domain for anti-parallel microtubule sliding.,Bodrug T, Wilson-Kubalek EM, Nithianantham S, Thompson AF, Alfieri A, Gaska I, Major J, Debs G, Inagaki S, Gutierrez P, Gheber L, McKenney RJ, Sindelar CV, Milligan R, Stumpff J, Rosenfeld SS, Forth ST, Al-Bassam J Elife. 2020 Jan 20;9. pii: 51131. doi: 10.7554/eLife.51131. PMID:31958056 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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