6CXI

Cardiac thin filament decorated with C0C1 fragment of cardiac myosin binding protein C mode 1

Summary for 6CXI

• Entry DOI: 10.2210/pdb6cxi/pdb
• EMDB information: 7780 7781
• Descriptor: Actin, cytoplasmic 2, Myosin-binding protein C, cardiac-type, Tropomyosin, ... (4 entities in total)
• Functional Keywords: myosin binding protein c, motor protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 20
• Total formula weight: 379114.31

Authors

Galkin, V.E.,Schroeder, G.F. (deposition date: 2018-04-03, release date: 2018-10-10, Last modification date: 2024-03-13)

Primary citation

Risi, C.,Belknap, B.,Forgacs-Lonart, E.,Harris, S.P.,Schroder, G.F.,White, H.D.,Galkin, V.E.
N-Terminal Domains of Cardiac Myosin Binding Protein C Cooperatively Activate the Thin Filament.
Structure, 26:1604-, 2018

PubMed Abstract: Muscle contraction relies on interaction between myosin-based thick filaments and actin-based thin filaments. Myosin binding protein C (MyBP-C) is a key regulator of actomyosin interactions. Recent studies established that the N'-terminal domains (NTDs) of MyBP-C can either activate or inhibit thin filaments, but the mechanism of their collective action is poorly understood. Cardiac MyBP-C (cMyBP-C) harbors an extra NTD, which is absent in skeletal isoforms of MyBP-C, and its role in regulation of cardiac contraction is unknown. Here we show that the first two domains of human cMyPB-C (i.e., C0 and C1) cooperate to activate the thin filament. We demonstrate that C1 interacts with tropomyosin via a positively charged loop and that this interaction, stabilized by the C0 domain, is required for thin filament activation by cMyBP-C. Our data reveal a mechanism by which cMyBP-C can modulate cardiac contraction and demonstrate a function of the C0 domain.

PubMed: 30270174
DOI: 10.1016/j.str.2018.08.007

Experimental method

ELECTRON MICROSCOPY (11 Å)