The calcium sensitizer drug MCI-154 binds the structural C-terminal domain of cardiac troponin C.

ABSTRACT: The compound MCI-154 was previously shown to increase the calcium sensitivity of cardiac muscle contraction. Using solution NMR spectroscopy, we demonstrate that MCI-154 interacts with the calcium-sensing subunit of the cardiac troponin complex, cardiac troponin C (cTnC). Surprisingly, however, it binds only to the structural C-terminal domain of cTnC (cCTnC), and not to the regulatory N-terminal domain (cNTnC) that determines the calcium sensitivity of cardiac muscle. Physiologically, cTnC is always bound to cardiac troponin I (cTnI), so we examined its interaction with MCI-154 in the presence of two soluble constructs, cTnI_1-77 and cTnI_135-209, which contain all of the segments of cTnI known to interact with cTnC. Neither the cTnC-cTnI_1-77 complex nor the

SUBMITTER: Li MX 

PROVIDER: S-EPMC6218639 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature