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Title | N-Terminal Domains of Cardiac Myosin Binding Protein C Cooperatively Activate the Thin Filament. |
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Journal, issue, pages | Structure, Vol. 26, Issue 12, Page 1604-11611.e4, Year 2018 |
Publish date | Dec 4, 2018 |
Authors | Cristina Risi / Betty Belknap / Eva Forgacs-Lonart / Samantha P Harris / Gunnar F Schröder / Howard D White / Vitold E Galkin / |
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 ...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. |
External links | Structure / PubMed:30270174 / PubMed Central |
Methods | EM (helical sym.) |
Resolution | 9.0 - 11.0 Å |
Structure data | EMDB-4346, PDB-6g2t: |
Source |
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Keywords | MOTOR PROTEIN / myosin binding protein C / CONTRACTILE PROTEIN / Cardiac thin filament regulator |