Deacon, John C. and Bloemink, Marieke J. and Rezavandi, Heresh and Geeves, Michael A. and Leinwand, Leslie 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. (doi:10.1007/s00018-012-0927-3) (Full text available)
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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.
|Uncontrolled keywords:||Muscle, Kinetics, ATPase, Contraction, Heart|
|Divisions:||Faculties > Sciences > School of Biosciences|
|Depositing User:||Sue Davies|
|Date Deposited:||20 Jun 2012 14:28 UTC|
|Last Modified:||20 May 2014 15:40 UTC|
|Resource URI:||https://kar.kent.ac.uk/id/eprint/29670 (The current URI for this page, for reference purposes)|
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