6G2T

human cardiac myosin binding protein C C1 Ig-domain bound to native cardiac thin filament

Summary for 6G2T

• Entry DOI: 10.2210/pdb6g2t/pdb
• EMDB information: 4346
• Descriptor: Actin, cytoplasmic 2, Myosin-binding protein C, cardiac-type, Tropomyosin (3 entities in total)
• Functional Keywords: cardiac thin filament regulator, contractile protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 16
• Total formula weight: 370146.14

Authors

Risi, C.,Belknap, B.,Forgacs, E.,Harris, S.P.,Schroder, G.F.,White, H.D.,Galkin, V.E. (deposition date: 2018-03-23, release date: 2018-10-17, Last modification date: 2024-05-15)

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, 26:1604-1611.e4, 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 (9 Å)