Myosin-binding protein C regulates the sarcomere lattice and stabilizes the OFF states of myosin heads

Anthony L. Hessel; Nichlas M. Engels; Michel N. Kuehn; Devin Nissen; Rachel L. Sadler; Weikang Ma; Thomas C. Irving; Wolfgang A. Linke; Samantha P. Harris

doi:10.1038/s41467-024-46957-7

Myosin-binding protein C regulates the sarcomere lattice and stabilizes the OFF states of myosin heads

Anthony L. Hessel, Nichlas M. Engels, Michel N. Kuehn, Devin Nissen, Rachel L. Sadler, Weikang Ma, Thomas C. Irving, Wolfgang A. Linke, Samantha P. Harris

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

2 Scopus citations

Abstract

Muscle contraction is produced via the interaction of myofilaments and is regulated so that muscle performance matches demand. Myosin-binding protein C (MyBP-C) is a long and flexible protein that is tightly bound to the thick filament at its C-terminal end (MyBP-C^C8C10), but may be loosely bound at its middle- and N-terminal end (MyBP-C^C1C7) to myosin heads and/or the thin filament. MyBP-C is thought to control muscle contraction via the regulation of myosin motors, as mutations lead to debilitating disease. We use a combination of mechanics and small-angle X-ray diffraction to study the immediate and selective removal of the MyBP-C^C1C7 domains of fast MyBP-C in permeabilized skeletal muscle. We show that cleavage leads to alterations in crossbridge kinetics and passive structural signatures of myofilaments that are indicative of a shift of myosin heads towards the ON state, highlighting the importance of MyBP-C^C1C7 to myofilament force production and regulation.

Original language	English (US)
Article number	2628
Journal	Nature communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-46957-7
State	Published - Dec 2024
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/s41467-024-46957-7

Cite this

@article{0d531f51822d43bcbdb8d9d6a13b9aab,

title = "Myosin-binding protein C regulates the sarcomere lattice and stabilizes the OFF states of myosin heads",

abstract = "Muscle contraction is produced via the interaction of myofilaments and is regulated so that muscle performance matches demand. Myosin-binding protein C (MyBP-C) is a long and flexible protein that is tightly bound to the thick filament at its C-terminal end (MyBP-CC8C10), but may be loosely bound at its middle- and N-terminal end (MyBP-CC1C7) to myosin heads and/or the thin filament. MyBP-C is thought to control muscle contraction via the regulation of myosin motors, as mutations lead to debilitating disease. We use a combination of mechanics and small-angle X-ray diffraction to study the immediate and selective removal of the MyBP-CC1C7 domains of fast MyBP-C in permeabilized skeletal muscle. We show that cleavage leads to alterations in crossbridge kinetics and passive structural signatures of myofilaments that are indicative of a shift of myosin heads towards the ON state, highlighting the importance of MyBP-CC1C7 to myofilament force production and regulation.",

author = "Hessel, {Anthony L.} and Engels, {Nichlas M.} and Kuehn, {Michel N.} and Devin Nissen and Sadler, {Rachel L.} and Weikang Ma and Irving, {Thomas C.} and Linke, {Wolfgang A.} and Harris, {Samantha P.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41467-024-46957-7",

language = "English (US)",

volume = "15",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Myosin-binding protein C regulates the sarcomere lattice and stabilizes the OFF states of myosin heads

AU - Hessel, Anthony L.

AU - Engels, Nichlas M.

AU - Kuehn, Michel N.

AU - Nissen, Devin

AU - Sadler, Rachel L.

AU - Ma, Weikang

AU - Irving, Thomas C.

AU - Linke, Wolfgang A.

AU - Harris, Samantha P.

PY - 2024/12

Y1 - 2024/12

N2 - Muscle contraction is produced via the interaction of myofilaments and is regulated so that muscle performance matches demand. Myosin-binding protein C (MyBP-C) is a long and flexible protein that is tightly bound to the thick filament at its C-terminal end (MyBP-CC8C10), but may be loosely bound at its middle- and N-terminal end (MyBP-CC1C7) to myosin heads and/or the thin filament. MyBP-C is thought to control muscle contraction via the regulation of myosin motors, as mutations lead to debilitating disease. We use a combination of mechanics and small-angle X-ray diffraction to study the immediate and selective removal of the MyBP-CC1C7 domains of fast MyBP-C in permeabilized skeletal muscle. We show that cleavage leads to alterations in crossbridge kinetics and passive structural signatures of myofilaments that are indicative of a shift of myosin heads towards the ON state, highlighting the importance of MyBP-CC1C7 to myofilament force production and regulation.

AB - Muscle contraction is produced via the interaction of myofilaments and is regulated so that muscle performance matches demand. Myosin-binding protein C (MyBP-C) is a long and flexible protein that is tightly bound to the thick filament at its C-terminal end (MyBP-CC8C10), but may be loosely bound at its middle- and N-terminal end (MyBP-CC1C7) to myosin heads and/or the thin filament. MyBP-C is thought to control muscle contraction via the regulation of myosin motors, as mutations lead to debilitating disease. We use a combination of mechanics and small-angle X-ray diffraction to study the immediate and selective removal of the MyBP-CC1C7 domains of fast MyBP-C in permeabilized skeletal muscle. We show that cleavage leads to alterations in crossbridge kinetics and passive structural signatures of myofilaments that are indicative of a shift of myosin heads towards the ON state, highlighting the importance of MyBP-CC1C7 to myofilament force production and regulation.

UR - http://www.scopus.com/inward/record.url?scp=85188416997&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85188416997&partnerID=8YFLogxK

U2 - 10.1038/s41467-024-46957-7

DO - 10.1038/s41467-024-46957-7

M3 - Article

C2 - 38521794

AN - SCOPUS:85188416997

SN - 2041-1723

VL - 15

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 2628

ER -

Myosin-binding protein C regulates the sarcomere lattice and stabilizes the OFF states of myosin heads

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this