Neck-motor interactions trigger rotation of the kinesin stalk.

Scientific Reports
Hong-Lei LiuSharyn A Endow

Abstract

Rotation of the coiled-coil stalk of the kinesin-14 motors is thought to drive displacements or steps by the motor along microtubules, but the structural changes that trigger stalk rotation and the nucleotide state in which it occurs are not certain. Here we report a kinesin-14 neck mutant that releases ADP more slowly than wild type and shows weaker microtubule affinity, consistent with defective stalk rotation. Unexpectedly, crystal structures show the stalk fully rotated - neck-motor interactions destabilize the stalk, causing it to rotate and ADP to be released, and alter motor affinity for microtubules. A new structural pathway accounts for the coupling of stalk rotation - the force-producing stroke - to changes in motor affinity for nucleotide and microtubules. Sequential disruption of salt bridges that stabilize the unrotated stalk could cause the stalk to initiate and complete rotation in different nucleotide states.

References

Aug 26, 1998·Science·S A Endow, K W Waligora
Oct 31, 1998·Nature·E P SablinR J Fletterick
Apr 23, 1999·Biochemistry·D B StoneR A Mendelson
May 25, 2001·Nature·M KikkawaN Hirokawa
Jun 2, 2001·The EMBO Journal·M YunS A Endow
Nov 12, 2002·The EMBO Journal·Thomas G WendtAndreas Hoenger
Feb 28, 2004·The Journal of Biological Chemistry·Maia V VinogradovaRobert J Fletterick
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Dec 31, 2005·Nature·Nicholas F EndresRonald D Vale
Jan 11, 2008·Structure·Wonmuk HwangMartin Karplus
Dec 3, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ahmad S KhalilMatthew J Lang
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Maia V VinogradovaRobert J Fletterick
Dec 19, 2009·The Journal of Biological Chemistry·Courtney L ParkeDavid K Worthylake
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Jul 7, 2010·BMC Structural Biology·Elisabeth HeustonSharyn A Endow
Feb 4, 2011·Biophysical Chemistry·Mark A HallenSharyn A Endow
Sep 6, 2011·Biophysical Journal·Sirish Kaushik Lakkaraju, Wonmuk Hwang
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Aug 17, 2019·The Biochemical Journal·Jan LudwiczakAdam Jarmuła
Mar 18, 2020·Scientific Reports·Michał Świątek, Ewa Gudowska-Nowak
Jun 13, 2018·ACS Chemical Biology·Andrew R PopchockWeihong Qiu
Nov 20, 2021·Science Advances·April L SolonMichael A Cianfrocco

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Methods Mentioned

BETA
nucleotide exchange
FRET

Software Mentioned

COOT
Chimera
HKL2000
PHENIX
MolProbity

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