Cardiac myosin-binding protein C decorates F-actin: Implications for cardiac function

Andrew E. Whitten; Cy M. Jeffries; Samantha P. Harris; Jill Trewhella

doi:10.1073/pnas.0808903105

Cardiac myosin-binding protein C decorates F-actin: Implications for cardiac function

Andrew E. Whitten, Cy M. Jeffries, Samantha P. Harris, Jill Trewhella

Research output: Contribution to journal › Article › peer-review

93 Scopus citations

Abstract

Cardiac myosin-binding protein C (cMyBP-C) is an accessory protein of striated muscle sarcomeres that is vital for maintaining regular heart function. Its 4 N-terminal regulatory domains, C0-C1-m-C2 (C0C2), influence actin and myosin interactions, the basic contractile proteins of muscle. Using neutron contrast variation data, we have determined that C0C2 forms a repeating assembly with filamentous actin, where the C0 and C1 domains of C0C2 attach near the DNase I-binding loop and subdomain 1 of adjacent actin monomers. Direct interactions between the N terminus of cMyBP-C and actin thereby provide a mechanism to modulate the contractile cycle by affecting the regulatory state of the thin filament and its ability to interact with myosin.

Original language	English (US)
Pages (from-to)	18360-18365
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	105
Issue number	47
DOIs	https://doi.org/10.1073/pnas.0808903105
State	Published - Nov 25 2008
Externally published	Yes

Keywords

C protein
Familial hypertrophic cardiomypathy
Muscle regulation
Neutron contrast variation
Small-angle scattering

ASJC Scopus subject areas

General

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title = "Cardiac myosin-binding protein C decorates F-actin: Implications for cardiac function",

abstract = "Cardiac myosin-binding protein C (cMyBP-C) is an accessory protein of striated muscle sarcomeres that is vital for maintaining regular heart function. Its 4 N-terminal regulatory domains, C0-C1-m-C2 (C0C2), influence actin and myosin interactions, the basic contractile proteins of muscle. Using neutron contrast variation data, we have determined that C0C2 forms a repeating assembly with filamentous actin, where the C0 and C1 domains of C0C2 attach near the DNase I-binding loop and subdomain 1 of adjacent actin monomers. Direct interactions between the N terminus of cMyBP-C and actin thereby provide a mechanism to modulate the contractile cycle by affecting the regulatory state of the thin filament and its ability to interact with myosin.",

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T2 - Implications for cardiac function

AU - Whitten, Andrew E.

AU - Jeffries, Cy M.

AU - Harris, Samantha P.

AU - Trewhella, Jill

PY - 2008/11/25

Y1 - 2008/11/25

N2 - Cardiac myosin-binding protein C (cMyBP-C) is an accessory protein of striated muscle sarcomeres that is vital for maintaining regular heart function. Its 4 N-terminal regulatory domains, C0-C1-m-C2 (C0C2), influence actin and myosin interactions, the basic contractile proteins of muscle. Using neutron contrast variation data, we have determined that C0C2 forms a repeating assembly with filamentous actin, where the C0 and C1 domains of C0C2 attach near the DNase I-binding loop and subdomain 1 of adjacent actin monomers. Direct interactions between the N terminus of cMyBP-C and actin thereby provide a mechanism to modulate the contractile cycle by affecting the regulatory state of the thin filament and its ability to interact with myosin.

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KW - Neutron contrast variation

KW - Small-angle scattering

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ER -

Cardiac myosin-binding protein C decorates F-actin: Implications for cardiac function

Abstract

Keywords

ASJC Scopus subject areas

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