Modular Aspects of Kinesin Force Generation Machinery

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2013 May 14

PMID 23663840

Citations 21

Authors

William R Hesse

Miriam Steiner

Matthew L Wohlever

Roger D Kamm

Wonmuk Hwang

Matthew J Lang

Affiliations

Soon will be listed here.

Abstract

The motor head of kinesin carries out microtubule binding, ATP hydrolysis, and force generation. Despite a high level of sequence and structural conservation, subtle variations in subdomains of the motor head determine family-specific properties. In particular, both Kinesin-1 (Kin-1) and Kinesin-5 (Kin-5) walk processively to the microtubule plus-end, yet show distinct motility characteristics suitable for their functions. We studied chimeric Kin-1/Kin-5 constructs with a combination of single molecule motility assays and molecular dynamics simulations to demonstrate that Kin-5 possesses a force-generating element similar to Kin-1, i.e., the cover-neck bundle. Furthermore, the Kin-5 neck linker makes additional contacts with the core of the motor head via loop L13, which putatively compensates for the shorter cover-neck bundle of Kin-5. Our results indicate that Kin-1 is mechanically optimized for individual cargo transport, whereas Kin-5 does not necessarily maximize its mechanical performance. Its biochemical rates and enhanced force sensitivity may instead be beneficial for operation in a group of motors. Such variations in subdomains would be a strategy for achieving diversity in motility with the conserved motor head.

Citing Articles

A kinesin-1 variant reveals motor-induced microtubule damage in cells.

Budaitis B, Badieyan S, Yue Y, Blasius T, Reinemann D, Lang M Curr Biol. 2022; 32(11):2416-2429.e6.

PMID: 35504282 PMC: 9993403. DOI: 10.1016/j.cub.2022.04.020.

Pathogenic mutations in the kinesin-3 motor KIF1A diminish force generation and movement through allosteric mechanisms.

Budaitis B, Jariwala S, Rao L, Yue Y, Sept D, Verhey K J Cell Biol. 2021; 220(4).

PMID: 33496723 PMC: 7844421. DOI: 10.1083/jcb.202004227.

Kinesin-5 Associates With the Spindle Apparatus During Cell Division and Is Important for Efficient Production of Infectious Sporozoites.

Zeeshan M, Brady D, Stanway R, Moores C, Holder A, Tewari R Front Cell Infect Microbiol. 2020; 10:583812.

PMID: 33154955 PMC: 7591757. DOI: 10.3389/fcimb.2020.583812.

How Kinesin-1 Utilize the Energy of Nucleotide: The Conformational Changes and Mechanochemical Coupling in the Unidirectional Motion of Kinesin-1.

Qin J, Zhang H, Geng Y, Ji Q Int J Mol Sci. 2020; 21(18).

PMID: 32972035 PMC: 7555842. DOI: 10.3390/ijms21186977.

The mechanochemistry of the kinesin-2 KIF3AC heterodimer is related to strain-dependent kinetic properties of KIF3A and KIF3C.

Bensel B, Woody M, Pyrpassopoulos S, Goldman Y, Gilbert S, Ostap E Proc Natl Acad Sci U S A. 2020; 117(27):15632-15641.

PMID: 32571914 PMC: 7354928. DOI: 10.1073/pnas.1916343117.

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