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Identification of sequence changes in myosin II that adjust muscle contraction velocity

Johnson, Chloe A., McGreig, Jake E., Jeanfavre, Sarah T., Walklate, Jonathan, Vera, Carlos D., Farré, Marta, Mulvihill, Daniel P., Baines, Anthony J., Ridout, Martin, Leinwand, Leslie A., and others. (2021) Identification of sequence changes in myosin II that adjust muscle contraction velocity. PLoS Biology, 19 (6). Article Number 3001248. ISSN 1544-9173. E-ISSN 1545-7885. (doi:10.1371/journal.pbio.3001248) (KAR id:89028)

Abstract

The speed of muscle contraction is related to body size; muscles in larger species contract at slower rates. Since contraction speed is a property of the myosin isoform expressed in a muscle, we investigated how sequence changes in a range of muscle myosin II isoforms enable this slower rate of muscle contraction. We considered 798 sequences from 13 mammalian myosin II isoforms to identify any adaptation to increasing body mass. We identified a correlation between body mass and sequence divergence for the motor domain of the 4 major adult myosin II isoforms (β/Type I, IIa, IIb, and IIx), suggesting that these isoforms have adapted to increasing body mass. In contrast, the non-muscle and developmental isoforms show no correlation of sequence divergence with body mass. Analysis of the motor domain sequence of β-myosin (predominant myosin in Type I/slow and cardiac muscle) from 67 mammals from 2 distinct clades identifies 16 sites, out of 800, associated with body mass (padj < 0.05) but not with the clade (padj > 0.05). Both clades change the same small set of amino acids, in the same order from small to large mammals, suggesting a limited number of ways in which contraction velocity can be successfully manipulated. To test this relationship, the 9 sites that differ between human and rat were mutated in the human β-myosin to match the rat sequence. Biochemical analysis revealed that the rat–human β-myosin chimera functioned like the native rat myosin with a 2-fold increase in both motility and in the rate of ADP release from the actin–myosin crossbridge (the step that limits contraction velocity). Thus, these sequence changes indicate adaptation of β-myosin as species mass increased to enable a reduced contraction velocity and heart rate.

Item Type: Article
DOI/Identification number: 10.1371/journal.pbio.3001248
Uncontrolled keywords: myosins; mammals; muscle contraction; phytogenetic analysis; amino acid analysis; cardiac muscles; protein sequencing; cardiomyopathies
Subjects: Q Science > Q Science (General)
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Mark Wass
Date Deposited: 05 Jul 2021 14:12 UTC
Last Modified: 14 Nov 2022 23:12 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/89028 (The current URI for this page, for reference purposes)

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