TY  - JOUR
AU  - Risi, Cristina
AU  - Belknap, Betty
AU  - Forgacs-Lonart, Eva
AU  - Harris, Samantha P.
AU  - Schröder, Gunnar
AU  - White, Howard D.
AU  - Galkin, Vitold E.
TI  - N-Terminal Domains of Cardiac Myosin Binding Protein C Cooperatively Activate the Thin Filament
JO  - Structure
VL  - 26
IS  - 12
SN  - 0969-2126
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - FZJ-2018-06302
SP  - 1604-1611.e4
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30270174
UR  - <Go to ISI:>//WOS:000454803300007
DO  - DOI:10.1016/j.str.2018.08.007
UR  - https://juser.fz-juelich.de/record/857021
ER  -