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TitleN-Terminal Domains of Cardiac Myosin Binding Protein C Cooperatively Activate the Thin Filament.
Journal, issue, pagesStructure, Vol. 26, Issue 12, Page 1604-11611.e4, Year 2018
Publish dateDec 4, 2018
AuthorsCristina Risi / Betty Belknap / Eva Forgacs-Lonart / Samantha P Harris / Gunnar F Schröder / Howard D White / Vitold E Galkin /
PubMed AbstractMuscle 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 linksStructure / PubMed:30270174 / PubMed Central
MethodsEM (helical sym.)
Resolution9.0 - 11.0 Å
Structure data

4346

6g2t

EMDB-4346, PDB-6g2t:
human cardiac myosin binding protein C C1 Ig-domain bound to native cardiac thin filament
Method: EM (helical sym.) / Resolution: 9.0 Å

7780

6cxi

EMDB-7780, PDB-6cxi:
Cardiac thin filament decorated with C0C1 fragment of cardiac myosin binding protein C mode 1
Method: EM (helical sym.) / Resolution: 11.0 Å

7781

6cxj

EMDB-7781, PDB-6cxj:
Cardiac thin filament decorated with C0C1 fragment of cardiac myosin binding protein C mode 2
Method: EM (helical sym.) / Resolution: 11.0 Å

Source
  • homo sapiens (human)
  • sus scrofa (pig)
KeywordsMOTOR PROTEIN / myosin binding protein C / CONTRACTILE PROTEIN / Cardiac thin filament regulator

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