Modeling Processive Motion of Kinesin-13 MCAK and Kinesin-14 Cik1-Kar3 Molecular Motors

Overview

Journal Protein Sci

Specialty Biochemistry

Date 2021 Aug 12

PMID 34382258

Citations 3

Authors

Ping Xie

Affiliations

Soon will be listed here.

Abstract

Kinesin-13 MCAK, which is composed of two identical motor domains, can undergo unbiased one-dimensional diffusion on microtubules. Kinesin-14 Cik1-Kar3, which is composed of a Kar3 motor domain and a Cik1 motor homology domain with no ATPase activity, can move processively toward the minus end of microtubules. Here, we present a model for the diffusion of MCAK homodimer and a model for the processive motion of Cik1-Kar3 heterodimer. Although the two dimeric motors show different domain composition, in the models it is proposed that the two motors use the similar physical mechanism to move processively. With the models, the dynamics of the two dimers is studied analytically. The theoretical results for MCAK reproduce quantitatively the available experimental data about diffusion constant and lifetime of the motor bound to microtubule in different nucleotide states. The theoretical results for Cik1-Kar3 reproduce quantitatively the available experimental data about load dependence of velocity and explain consistently the available experimental data about effects of the exchange and mutation of the motor homology domain on the velocity of the heterodimer. Moreover, predicted results for other aspects of the dynamics of the two dimers are provided.

Citing Articles

Biased movement of monomeric kinesin-3 KLP-6 explained by a symmetric Brownian ratchet model.

Kita T, Sasaki K, Niwa S Biophys J. 2024; 124(1):205-214.

PMID: 39604259 PMC: 11739925. DOI: 10.1016/j.bpj.2024.11.3312.

Modeling study of kinesin-13 MCAK microtubule depolymerase.

Xie P Eur Biophys J. 2024; 53(5-6):339-354.

PMID: 39093405 DOI: 10.1007/s00249-024-01718-8.

Modeling Studies of the Mechanism of Context-Dependent Bidirectional Movements of Kinesin-14 Motors.

Xie P Molecules. 2024; 29(8).

PMID: 38675612 PMC: 11055046. DOI: 10.3390/molecules29081792.

Modeling processive motion of kinesin-13 MCAK and kinesin-14 Cik1-Kar3 molecular motors.

Xie P Protein Sci. 2021; 30(10):2092-2105.

PMID: 34382258 PMC: 8442974. DOI: 10.1002/pro.4165.

References

Mieck C, Molodtsov M, Drzewicka K, van der Vaart B, Litos G, Schmauss G . Non-catalytic motor domains enable processive movement and functional diversification of the kinesin-14 Kar3. Elife. 2015; 4. PMC: 4338441. DOI: 10.7554/eLife.04489. View

Guo S, Xie P . A common chemomechanical coupling model for orphan and conventional kinesin molecular motors. Biophys Chem. 2020; 264:106427. DOI: 10.1016/j.bpc.2020.106427. View

Meluh P, Rose M . KAR3, a kinesin-related gene required for yeast nuclear fusion. Cell. 1990; 60(6):1029-41. DOI: 10.1016/0092-8674(90)90351-e. View

Hoenger A, Milligan R . Motor domains of kinesin and ncd interact with microtubule protofilaments with the same binding geometry. J Mol Biol. 1997; 265(5):553-64. DOI: 10.1006/jmbi.1996.0757. View

Lawrence C, Dawe R, Christie K, Cleveland D, Dawson S, Endow S . A standardized kinesin nomenclature. J Cell Biol. 2004; 167(1):19-22. PMC: 2041940. DOI: 10.1083/jcb.200408113. View

Allingham J, Sproul L, Rayment I, Gilbert S . Vik1 modulates microtubule-Kar3 interactions through a motor domain that lacks an active site. Cell. 2007; 128(6):1161-72. PMC: 1987336. DOI: 10.1016/j.cell.2006.12.046. View

Hoenger A, Sablin E, Vale R, Fletterick R, Milligan R . Three-dimensional structure of a tubulin-motor-protein complex. Nature. 1995; 376(6537):271-4. DOI: 10.1038/376271a0. View

Fink G, Hajdo L, Skowronek K, Reuther C, Kasprzak A, Diez S . The mitotic kinesin-14 Ncd drives directional microtubule-microtubule sliding. Nat Cell Biol. 2009; 11(6):717-23. DOI: 10.1038/ncb1877. View

Okada Y, Hirokawa N . A processive single-headed motor: kinesin superfamily protein KIF1A. Science. 1999; 283(5405):1152-7. DOI: 10.1126/science.283.5405.1152. View

10.

Xie P . Non-tight and tight chemomechanical couplings of biomolecular motors under hindering loads. J Theor Biol. 2020; 490:110173. DOI: 10.1016/j.jtbi.2020.110173. View

11.

Wordeman L, Mitchison T . Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis. J Cell Biol. 1995; 128(1-2):95-104. PMC: 2120339. DOI: 10.1083/jcb.128.1.95. View

12.

Xie P, Guo S, Chen H . ATP-Concentration- and Force-Dependent Chemomechanical Coupling of Kinesin Molecular Motors. J Chem Inf Model. 2018; 59(1):360-372. DOI: 10.1021/acs.jcim.8b00577. View

13.

Vu H, Chakrabarti S, Hinczewski M, Thirumalai D . Discrete Step Sizes of Molecular Motors Lead to Bimodal Non-Gaussian Velocity Distributions under Force. Phys Rev Lett. 2016; 117(7):078101. DOI: 10.1103/PhysRevLett.117.078101. View

14.

Guo S, Shi X, Wang P, Xie P . Run length distribution of dimerized kinesin-3 molecular motors: comparison with dimeric kinesin-1. Sci Rep. 2019; 9(1):16973. PMC: 6861319. DOI: 10.1038/s41598-019-53550-2. View

15.

Miki H, Okada Y, Hirokawa N . Analysis of the kinesin superfamily: insights into structure and function. Trends Cell Biol. 2005; 15(9):467-76. DOI: 10.1016/j.tcb.2005.07.006. View

16.

Chu H, Yun M, Anderson D, Sage H, Park H, Endow S . Kar3 interaction with Cik1 alters motor structure and function. EMBO J. 2005; 24(18):3214-23. PMC: 1224680. DOI: 10.1038/sj.emboj.7600790. View

17.

Lowe J, Li H, Downing K, Nogales E . Refined structure of alpha beta-tubulin at 3.5 A resolution. J Mol Biol. 2001; 313(5):1045-57. DOI: 10.1006/jmbi.2001.5077. View

18.

Guo S, Shi X, Wang P, Xie P . Processivity of dimeric kinesin-1 molecular motors. FEBS Open Bio. 2018; 8(8):1332-1351. PMC: 6070657. DOI: 10.1002/2211-5463.12486. View

19.

Duan Z, Xie P, Li W, Wang P . Are coiled-coils of dimeric kinesins unwound during their walking on microtubule?. PLoS One. 2012; 7(4):e36071. PMC: 3338639. DOI: 10.1371/journal.pone.0036071. View

20.

Maney T, Wagenbach M, Wordeman L . Molecular dissection of the microtubule depolymerizing activity of mitotic centromere-associated kinesin. J Biol Chem. 2001; 276(37):34753-8. DOI: 10.1074/jbc.M106626200. View