Modular aspects of kinesin force generation machinery.

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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Hesse WR,Steiner M,Wohlever ML,Kamm RD,Hwang W,Lang MJ

doi

10.1016/j.bpj.2013.03.051

subject

Has Abstract

pub_date

2013-05-07 00:00:00

pages

1969-78

issue

9

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(13)00390-1

journal_volume

104

pub_type

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