Locking Function of a Key Residue in Kinesin's Gating Mechanism

doi:10.1088/0256-307X/31/4/048702

Chin. Phys. Lett.

2014, Vol. 31

Issue (04): 048702 DOI: 10.1088/0256-307X/31/4/048702

CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY

Locking Function of a Key Residue in Kinesin's Gating Mechanism

GENG Yi-Zhao¹, ZHANG Hui², JI Qing^2,3**, YAN Shi-Wei^1**

¹College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875
²School of Science, Hebei University of Technology, Tianjin 300401
³Institute of Biophysics, Hebei University of Technology, Tianjin 300401

Cite this article:

GENG Yi-Zhao, ZHANG Hui, JI Qing et al 2014 Chin. Phys. Lett. 31 048702

Download: PDF(1177KB)
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract In kinesin's mechanochemical cycle, ATP's binding to the nucleotide-free leading head is exquisitely gated so that futile hydrolysis is effectively avoided. Experiments show that, when both kinesin heads bind to a microtubule, ATP cannot bind to kinesin's leading head when the neck linker (NL) of this head has a backward orientation. How NL's backward orientation is maintained needs understanding on a structural basis. By using steered molecular dynamics and mutation simulations, we investigate the backward-pointing conformation of the leading head's NL under different inter-head tensions. We find that the NL cannot keep in a strict backward orientation solely by the inter-head tension. LYS325 (amino acid sequence in 2KIN) has an assistant locking function which locks the NL and β0 to the β-domain. This locking function has an enhanced positive cooperation with the inter-head tension. When the inter-head tension is weakened, this locking function can be broken, resulting in a loose backward orientation of the NL. The difference between the strict and loose backward orientation of the NL might be a crucial factor in the gating mechanism. These results are consistent with relevant experiments and proposals.

Received: 14 November 2013 Published: 25 March 2014

PACS:	87.16.Nn	(Motor proteins (myosin, kinesin dynein))
	87.10.Tf	(Molecular dynamics simulation)
	87.15.hp	(Conformational changes)

TRENDMD:

URL:

https://cpl.iphy.ac.cn/10.1088/0256-307X/31/4/048702 OR https://cpl.iphy.ac.cn/Y2014/V31/I04/048702

Service
	E-mail this article
	E-mail Alert
	RSS
Articles by authors
	GENG Yi-Zhao
	ZHANG Hui
	JI Qing
	YAN Shi-Wei

[1] Lawrence C J et al 2004 J. Cell Biol. 167 19
[2] Vale R D 2003 Cell 112 467
[3] Svoboda K et al 1993 Nature 365 721
[4] Hirokawa N et al 2009 Nat. Rev. Mol. Cell Biol. 10 682
[5] Rice S et al 1999 Nature 402 778
[6] Vale R D and Milligan R A 2000 Science 288 88
[7] Tomishige M et al 2006 Nat. Struct. Mol. Biol. 13 887
[8] Sablin E P and Fletterick R J 2004 J. Biol. Chem. 279 15707
[9] Block S M 2007 Biophys. J. 92 2986
[10] Valentine M T and Gillbert S P 2007 Curr. Opin. Cell Biol. 19 75
[11] Hua W et al 1997 Nature 388 390
[12] Schnitzer M J and Block S M 1997 Nature 388 386
[13] Coy D L, Wagenbach M and Howard J 1999 J. Biol. Chem. 274 3667
[14] Berliner E et al 1995 Nature 373 718
[15] Hancock W O and Howard J 1998 J. Cell Biol. 140 1395
[16] Toprak E et al 2009 Proc. Natl. Acad. Sci. USA 106 12717
[17] Hariharan V and Hancock W 2009 Cell. Mol. Bioeng. 2 177
[18] Xie P 2010 Int. J. Biol. Sci. 6 665
[19] Rosenfeld S S et al 2002 J. Biol. Chem. 277 36731
[20] Rosenfeld S S et al 2003 J. Biol. Chem. 278 18550
[21] Uemura S and Ishiwata S 2003 Nat. Struct. Mol. Biol. 10 308
[22] Clancy B E et al 2011 Nat. Struct. Mol. Biol. 18 1020
[23] Xie P et al 2005 Chin. Phys. B 14 734
[24] Hancock W O and Howard J 1999 Proc. Natl. Acad. Sci. USA 96 13147
[25] Schief W R et al 2004 Proc. Natl. Acad. Sci. USA 101 1183
[26] Crevel I et al 2004 EMBO J. 23 23
[27] Geng Y Z et al 2014 Arch. Biochem. Biophys. 543 10
[28] Guydosh N R and Block S M 2006 Proc. Natl. Acad. Sci. USA 103 8054
[29] Yildiz A et al 2008 Cell 134 1030
[30] Shastry S and Hancock W O 2011 Proc. Natl. Acad. Sci. USA 108 16253
[31] Phillips J C et al 2005 J. Comput. Chem. 26 1781
[32] MacKerell A D et al 1998 J. Phys. Chem. B 102 3586
[33] Humphrey W et al 1996 J. Mol. Graphics 14 33
[34] Jorgensen W L et al 1983 J. Chem. Phys. 79 926
[35] Geng Y Z et al 2013 arXiv:1309.5173 [physics.bio-ph]
[36] Sack S et al 1997 Biochemistry 36 16155
[37] Jon Kull F et al 1996 Nature 380 550
[38] Geng Y Z et al 2014 Cell. Mol. Bioeng. 7 99
[39] Hwang W et al 2008 Structure 16 62
[40] Khalil A S et al 2008 Proc. Natl. Acad. Sci. USA 105 19247
[41] Walliams D H et al 2004 Angew. Chem. Int. Ed. 43 6596
[42] Mori T et al 2007 Nature 450 750
[43] Asenjo A B et al 2003 Nat. Struct. Mol. Biol. 10 836
[44] Sosa H et al 2001 Nat. Struct. Mol. Biol. 8 540
[45] Kikkawa M 2008 Trends Cell Biol. 18 128

Related articles from Frontiers Journals

[1]	Yu-Ru Liu, Peng-Ye Wang, Wei Li, and Ping Xie. Acceleration of DNA Replication of Klenow Fragment by Small Resisting Force[J]. Chin. Phys. Lett., 2021, 38(11): 048702
[2]	Yi-Zhao Geng, Hui Zhang, Gang Lyu, Qing Ji. Initiation Mechanism of Kinesin's Neck Linker Docking Process[J]. Chin. Phys. Lett., 2017, 34(2): 048702
[3]	HUANG Yan-Bin, PAN Zhang, ZHANG Hui, AN Li, KONG De-Xin, JI Qing. Water in the Neck-Zipper Region of Kinesin[J]. Chin. Phys. Lett., 2009, 26(7): 048702
[4]	SUN Lian-Xiu. Rectification Efficiency of Two Harmonically Coupled Particles[J]. Chin. Phys. Lett., 2009, 26(4): 048702
[5]	WANG Hong, DOU Shuo-Xing, WANG Peng-Ye. Monte Carlo Simulation on Coordinated Movement of Kinesin and Dynein Motors[J]. Chin. Phys. Lett., 2008, 25(1): 048702
[6]	WANG Hong, DOU Shuo-Xing, WANG Peng-Ye. Monte Carlo Simulation of Kinesin Movement with a Lattice Model[J]. Chin. Phys. Lett., 2005, 22(11): 048702
[7]	GAO De, JI Qing, Lü Gang. How Is a Protein Molecule Nearsighted?[J]. Chin. Phys. Lett., 2005, 22(9): 048702
[8]	FENG Juan, ZHUO Yi-Zhong,. Master Equation Approach to Molecular Motor’s Directed Motion[J]. Chin. Phys. Lett., 2005, 22(2): 048702

Viewed

Full text

Abstract