Computational Methods Elucidate Consequences of Mutations and Post-translational Modifications on Troponin I Effective Concentration to Troponin C.

ABSTRACT: Ca²⁺ binding to cardiac troponin C (cTnC) causes a conformational shift that exposes a hydrophobic patch (cTnC_HP) for binding of the cTnI switch peptide (cTnI_SP), ultimately resulting in contraction of the heart. The inhibitory peptide (cTnI_IP), attached at the N-terminal end of the cTnI_SP, serves as a tether for the cTnI_SP to the rest of the troponin complex. Due to this tethered nature, the cTnI_SP remains within proximity of the hydrophobic patch region, resulting in the cTnC_HP experiencing an elevated "effective concentration" of the cTnI_SP. Mutations to the cTnI_IP region have been hypothesized to cause disease by affecting the ability of the cTnI_SP to "find" the hydr

SUBMITTER: Cool AM 

PROVIDER: S-EPMC8341295 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature