Literature DB >> 20160108

An atomic-level mechanism for activation of the kinesin molecular motors.

Charles V Sindelar1, Kenneth H Downing.   

Abstract

Kinesin cytoskeletal motors convert the energy of ATP hydrolysis into stepping movement along microtubules. A partial model of this process has been derived from crystal structures, which show that movement of the motor domain relative to its major microtubule binding element, the switch II helix, is coupled to docking of kinesin's neck linker element along the motor domain. This docking would displace the cargo in the direction of travel and so contribute to a step. However, the crystal structures do not reveal how ATP binding and hydrolysis govern this series of events. We used cryoelectron microscopy to derive 8-9 A-resolution maps of four nucleotide states encompassing the microtubule-attached kinetic cycle of a kinesin motor. The exceptionally high quality of these maps allowed us to build in crystallographically determined conformations of kinesin's key subcomponents, yielding novel arrangements of kinesin's switch II helix and nucleotide-sensing switch loops. The resulting atomic models reveal a seesaw mechanism in which the switch loops, triggered by ATP binding, propel their side of the motor domain down and thereby elicit docking of the neck linker on the opposite side of the seesaw. Microtubules engage the seesaw mechanism by stabilizing the formation of extra turns at the N terminus of the switch II helix, which then serve as an anchor for the switch loops as they modulate the seesaw angle. These observations explain how microtubules activate kinesin's ATP-sensing machinery to promote cargo displacement and inform the mechanism of kinesin's ancestral relative, myosin.

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Year:  2010        PMID: 20160108      PMCID: PMC2840164          DOI: 10.1073/pnas.0911208107

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  31 in total

1.  A structural change in the kinesin motor protein that drives motility.

Authors:  S Rice; A W Lin; D Safer; C L Hart; N Naber; B O Carragher; S M Cain; E Pechatnikova; E M Wilson-Kubalek; M Whittaker; E Pate; R Cooke; E W Taylor; R A Milligan; R D Vale
Journal:  Nature       Date:  1999-12-16       Impact factor: 49.962

2.  Closing of the nucleotide pocket of kinesin-family motors upon binding to microtubules.

Authors:  Nariman Naber; Todd J Minehardt; Sarah Rice; Xiaoru Chen; Jean Grammer; Marija Matuska; Ronald D Vale; Peter A Kollman; Roberto Car; Ralph G Yount; Roger Cooke; Edward Pate
Journal:  Science       Date:  2003-05-02       Impact factor: 47.728

3.  A structural state of the myosin V motor without bound nucleotide.

Authors:  Pierre-Damien Coureux; Amber L Wells; Julie Ménétrey; Christopher M Yengo; Carl A Morris; H Lee Sweeney; Anne Houdusse
Journal:  Nature       Date:  2003-09-25       Impact factor: 49.962

4.  UCSF Chimera--a visualization system for exploratory research and analysis.

Authors:  Eric F Pettersen; Thomas D Goddard; Conrad C Huang; Gregory S Couch; Daniel M Greenblatt; Elaine C Meng; Thomas E Ferrin
Journal:  J Comput Chem       Date:  2004-10       Impact factor: 3.376

5.  Kinesin's second step.

Authors:  Lisa M Klumpp; Andreas Hoenger; Susan P Gilbert
Journal:  Proc Natl Acad Sci U S A       Date:  2004-02-25       Impact factor: 11.205

Review 6.  The role of microtubules in processive kinesin movement.

Authors:  Masahide Kikkawa
Journal:  Trends Cell Biol       Date:  2008-02-15       Impact factor: 20.808

7.  9-Angström structure of a microtubule-bound mitotic motor.

Authors:  Andrew J Bodey; Masahide Kikkawa; Carolyn A Moores
Journal:  J Mol Biol       Date:  2009-03-10       Impact factor: 5.469

8.  ATP hydrolysis in Eg5 kinesin involves a catalytic two-water mechanism.

Authors:  Courtney L Parke; Edward J Wojcik; Sunyoung Kim; David K Worthylake
Journal:  J Biol Chem       Date:  2009-12-15       Impact factor: 5.157

9.  Rigor-like structures from muscle myosins reveal key mechanical elements in the transduction pathways of this allosteric motor.

Authors:  Yuting Yang; S Gourinath; Mihály Kovács; László Nyitray; Robbie Reutzel; Daniel M Himmel; Elizabeth O'Neall-Hennessey; Ludmilla Reshetnikova; Andrew G Szent-Györgyi; Jerry H Brown; Carolyn Cohen
Journal:  Structure       Date:  2007-05       Impact factor: 5.006

Review 10.  On the myosin catalysis of ATP hydrolysis.

Authors:  Hirofumi Onishi; Naoki Mochizuki; Manuel F Morales
Journal:  Biochemistry       Date:  2004-04-06       Impact factor: 3.162

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  80 in total

1.  Multiple hindered rotators in a gyroscope-inspired tribenzylamine hemicryptophane.

Authors:  Najat S Khan; Jose Manuel Perez-Aguilar; Tara Kaufmann; P Aru Hill; Olena Taratula; One-Sun Lee; Patrick J Carroll; Jeffery G Saven; Ivan J Dmochowski
Journal:  J Org Chem       Date:  2011-01-27       Impact factor: 4.354

2.  Multiple conformations of the nucleotide site of Kinesin family motors in the triphosphate state.

Authors:  Nariman Naber; Adam Larson; Sarah Rice; Roger Cooke; Edward Pate
Journal:  J Mol Biol       Date:  2011-01-26       Impact factor: 5.469

3.  A structural perspective on the dynamics of kinesin motors.

Authors:  Changbong Hyeon; José N Onuchic
Journal:  Biophys J       Date:  2011-12-07       Impact factor: 4.033

4.  Insight into the molecular mechanism of the multitasking kinesin-8 motor.

Authors:  Carsten Peters; Katjuša Brejc; Lisa Belmont; Andrew J Bodey; Yan Lee; Ming Yu; Jun Guo; Roman Sakowicz; James Hartman; Carolyn A Moores
Journal:  EMBO J       Date:  2010-09-03       Impact factor: 11.598

5.  Kinesin motor activation: microtubules pull the switches.

Authors:  Franck Fourniol; Carolyn A Moores
Journal:  Proc Natl Acad Sci U S A       Date:  2010-02-17       Impact factor: 11.205

6.  The structure of the kinesin-1 motor-tail complex reveals the mechanism of autoinhibition.

Authors:  Hung Yi Kristal Kaan; David D Hackney; Frank Kozielski
Journal:  Science       Date:  2011-08-12       Impact factor: 47.728

Review 7.  An electron microscopy journey in the study of microtubule structure and dynamics.

Authors:  Eva Nogales
Journal:  Protein Sci       Date:  2015-10-11       Impact factor: 6.725

8.  Kinetics of nucleotide-dependent structural transitions in the kinesin-1 hydrolysis cycle.

Authors:  Keith J Mickolajczyk; Nathan C Deffenbaugh; Jaime Ortega Arroyo; Joanna Andrecka; Philipp Kukura; William O Hancock
Journal:  Proc Natl Acad Sci U S A       Date:  2015-12-16       Impact factor: 11.205

9.  The structural kinetics of switch-1 and the neck linker explain the functions of kinesin-1 and Eg5.

Authors:  Joseph M Muretta; Yonggun Jun; Steven P Gross; Jennifer Major; David D Thomas; Steven S Rosenfeld
Journal:  Proc Natl Acad Sci U S A       Date:  2015-11-16       Impact factor: 11.205

10.  Recurrent KIF5C mutation leading to frontal pachygyria without microcephaly.

Authors:  Mara Cavallin; Laurence Hubert; Vincent Cantagrel; Arnold Munnich; Nathalie Boddaert; Catherine Vincent-Delorme; Jean Christophe Cuvellier; Cecile Masson; Claude Besmond; Nadia Bahi-Buisson
Journal:  Neurogenetics       Date:  2015-09-19       Impact factor: 2.660

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