Comprehensive structural model of the mechanochemical cycle of a mitotic motor highlights molecular adaptations in the kinesin family

Please use this identifier to cite or link to this item: https://ir.lib.ncu.edu.tw/handle/987654321/104381

Title:	Comprehensive structural model of the mechanochemical cycle of a mitotic motor highlights molecular adaptations in the kinesin family
Authors:	田溶根;Goulet, Adeline;Major, Jennifer;Jun, Yonggun;Gross, Steven P.;Rosenfeld, Steven S.;Moores, Carolyn A.
Contributors:	理學院物理學系
Keywords:	Active sites;Adenosine Diphosphate - metabolism;Adenosine triphosphatase;Adenosine triphosphatases;Adenosine Triphosphate - metabolism;ATP;Biological Sciences;Biophysics and Computational Biology;Cancer;Cell division;Cellular biology;Dimers;Humans;Hydrolysis;Kinesin - chemistry;Kinesin - metabolism;Kinetics;Life Sciences;Microtubules - metabolism;Mitosis;Models, Molecular;Motor ability;Motors;Nucleotides;Protein Binding;Protein Structure, Tertiary;Retraining;Sequence Deletion;Structure-Activity Relationship;Surface contours
Date:	2014-02-04
Issue Date:	2026-04-23 11:49:10 (UTC+8)
Publisher:	National Academy of Sciences;United States: National Academy of Sciences
Abstract:	摘要： Kinesins are responsible for a wide variety of microtubule-based, ATP-dependent functions. Their motor domain drives these activities, but the molecular adaptations that specify these diverse and essential cellular activities are poorly understood. It has been assumed that the first identified kinesin—the transport motor kinesin-1—is the mechanistic paradigm for the entire superfamily, but accumulating evidence suggests otherwise. To address the deficits in our understanding of the molecular basis of functional divergence within the kinesin superfamily, we studied kinesin-5s, which are essential mitotic motors whose inhibition blocks cell division. Using cryo-electron microscopy and determination of structure at subnanometer resolution, we have visualized conformations of microtubule-bound human kinesin-5 motor domain at successive steps in its ATPase cycle. After ATP hydrolysis, nucleotide-dependent conformational changes in the active site are allosterically propagated into rotations of the motor domain and uncurling of the drug-binding loop L5. In addition, the mechanical neck-linker element that is crucial for motor stepping undergoes discrete, ordered displacements. We also observed large reorientations of the motor N terminus that indicate its importance for kinesin-5 function through control of neck-linker conformation. A kinesin-5 mutant lacking this N terminus is enzymatically active, and ATP-dependent neck-linker movement and motility are defective, although not ablated. All these aspects of kinesin-5 mechanochemistry are distinct from kinesin-1. Our findings directly demonstrate the regulatory role of the kinesin-5 N terminus in collaboration with the motor's structured neck-linker and highlight the multiple adaptations within kinesin motor domains that tune their mechanochemistries according to distinct functional requirements. 其他題名： Proc Natl Acad Sci USA 其他題名： Proc Natl Acad Sci U S A 出版者： United States: National Academy of Sciences 出版日期： 2014-02-04 出處： Proceedings of the National Academy of Sciences - PNAS, 2014-02, Vol.111 (5), p.1837-1842 資源來源： JSTOR Life Sciences Collection 版權： copyright © 1993–2008 National Academy of Sciences of the United States of America 版權： Copyright National Academy of Sciences Feb 4, 2014 版權： licence_http://creativecommons.org/publicdomain/zero 識別號： ISSN: 0027-8424 識別號： ISSN: 1091-6490 識別號： EISSN: 1091-6490 識別號： DOI: 10.1073/pnas.1319848111 識別號： PMID: 24449904
Appears in Collections:	[Department of Physics] journal & Dissertation

Files in This Item:

File	Description	Size	Format
index.html		0Kb	HTML	14	View/Open

社群 sharing

Loading...