Origins of Reversed Directionality in the Ncd Molecular Motor

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1994 Feb 15

PMID 8112290

Citations 24

Authors

A Lockhart

R A Cross

Affiliations

Soon will be listed here.

Abstract

The head or motor domain of the ncd (non-claret disjunctional) molecular motor is 41% identical to that of kinesin, yet moves along microtubules in the opposite direction to kinesin. We show here that despite the reversed directionality of ncd, its kinetics in solution are homologous in key respects to those of kinesin. The rate limiting step, ADP release, occurs at 0.0033 s-1 at 100 mM NaCl and is accelerated approximately 1000-fold when the motor binds to microtubules. Other reaction steps are all very fast (> 0.1 s-1) compared with ADP release, and the motor is consequently paused in the ncd.ADP state until microtubule binding occurs (Kd = 2 microM), at which point ADP release is triggered and the motor locks onto the microtubule in a rigor-like state. These data identify close functional homology between the strong binding states of kinesin and ncd, and in view of this we discuss a possible mechanism for directional reversal, in which the strong binding states of ncd and kinesin are functionally identical, but the weak binding states are biased in opposite directions.

Citing Articles

Tether-scanning the kinesin motor domain reveals a core mechanical action.

Sumiyoshi R, Yamagishi M, Furuta A, Nishizaka T, Furuta K, Cross R Proc Natl Acad Sci U S A. 2024; 121(30):e2403739121.

PMID: 39012822 PMC: 11287258. DOI: 10.1073/pnas.2403739121.

Discovery of 2-(3-Benzamidopropanamido)thiazole-5-carboxylate Inhibitors of the Kinesin HSET (KIFC1) and the Development of Cellular Target Engagement Probes.

Saint-Dizier F, Matthews T, Gregson A, Prevet H, McHardy T, Colombano G J Med Chem. 2023; 66(4):2622-2645.

PMID: 36749938 PMC: 9969401. DOI: 10.1021/acs.jmedchem.2c01591.

Alp7/TACC-Alp14/TOG generates long-lived, fast-growing MTs by an unconventional mechanism.

Hussmann F, Drummond D, Peet D, Martin D, Cross R Sci Rep. 2016; 6:20653.

PMID: 26864000 PMC: 4749977. DOI: 10.1038/srep20653.

Measuring collective transport by defined numbers of processive and nonprocessive kinesin motors.

Furuta K, Furuta A, Toyoshima Y, Amino M, Oiwa K, Kojima H Proc Natl Acad Sci U S A. 2012; 110(2):501-6.

PMID: 23267076 PMC: 3545764. DOI: 10.1073/pnas.1201390110.

Coupling of kinesin ATP turnover to translocation and microtubule regulation: one engine, many machines.

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PMID: 22447431 PMC: 3521643. DOI: 10.1007/s10974-012-9289-6.

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