Identification of functional differences between recombinant human α and β cardiac myosin motors

Deacon, J.C. and Bloemink, M.J. and Rezavandi, H. and Geeves, M.A. and Leinwand, L.A. (2012) Identification of functional differences between recombinant human α and β cardiac myosin motors. Cellular and Molecular Life Sciences, 69 (13). pp. 2261-2277. ISSN 1420-682X. (Full text available)

PDF - Published Version
Available under License Creative Commons Attribution.
Download (707kB) Preview
[img]
Preview
Official URL
http://dx.doi.org/10.1007/s00018-012-0927-3

Abstract

The myosin isoform composition of the heart is dynamic in health and disease and has been shown to affect contractile velocity and force generation. While different mammalian species express different proportions of a and b myosin heavy chain, healthy human heart ventricles express these isoforms in a ratio of about 1:9 (a:b) while failing human ventricles express no detectable a-myosin. We report here fast-kinetic analysis of recombinant human a and b myosin heavy chain motor domains. This represents the first such analysis of any human muscle myosin motor and the first of a-myosin from any species. Our findings reveal substantial isoform differences in individual kinetic parameters, overall contractile character, and predicted cycle times. For these parameters, a-subfragment 1 (S1) is far more similar to adult fast skeletal muscle myosin isoforms than to the slow b isoform despite 91% sequence identity between the motor domains of a- and b-myosin. Among the features that differentiate a- from b-S1: the ATP hydrolysis step of a-S1 is *ten-fold faster than b-S1, a-S1 exhibits *five-fold weaker actin affinity than b-S1, and actin a-S1 exhibits rapid ADP release, which is > tenfold faster than ADP release for b-S1. Overall, the cycle times are ten-fold faster for a-S1 but the portion of time each myosin spends tightly bound to actin (the duty ratio) is similar. Sequence analysis points to regions that might underlie the basis for this finding.

Item Type: Article
Uncontrolled keywords: Muscle, Kinetics, ATPase, Contraction, Heart
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Sue Davies
Date Deposited: 20 Jun 2012 14:28
Last Modified: 22 Jun 2012 12:02
Resource URI: http://kar.kent.ac.uk/id/eprint/29670 (The current URI for this page, for reference purposes)
  • Depositors only (login required):

Downloads

Downloads per month over past year