%0 Journal Article
%A Risi, Cristina
%A Belknap, Betty
%A Forgacs-Lonart, Eva
%A Harris, Samantha P.
%A Schröder, Gunnar
%A White, Howard D.
%A Galkin, Vitold E.
%T N-Terminal Domains of Cardiac Myosin Binding Protein C Cooperatively Activate the Thin Filament
%J Structure
%V 26
%N 12
%@ 0969-2126
%C Cambridge, Mass.
%I Cell Press
%M FZJ-2018-06302
%P 1604-1611.e4
%D 2018
%X Muscle contraction relies on interaction betweenmyosin-based thick filaments and actin-based thinfilaments. Myosin binding protein C (MyBP-C) is akey regulator of actomyosin interactions. Recentstudies established that the N0-terminal domains(NTDs) of MyBP-C can either activate or inhibit thinfilaments, but the mechanism of their collectiveaction is poorly understood. Cardiac MyBP-C(cMyBP-C) harbors an extra NTD, which is absentin skeletal isoforms of MyBP-C, and its role in regulationof cardiac contraction is unknown. Here weshow 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 tropomyosinvia a positively charged loop and that thisinteraction, stabilized by the C0 domain, is requiredfor thin filament activation by cMyBP-C. Our datareveal a mechanism by which cMyBP-C can modulatecardiac contraction and demonstrate a function of the C0 domain.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30270174
%U <Go to ISI:>//WOS:000454803300007
%R 10.1016/j.str.2018.08.007
%U https://juser.fz-juelich.de/record/857021