Modulation of cardiac thin filament structure by phosphorylated troponin-I analyzed by protein-protein docking and molecular dynamics simulation.

ABSTRACT: Tropomyosin, controlled by troponin-linked Ca²⁺-binding, regulates muscle contraction by a macromolecular scale steric-mechanism that governs myosin-crossbridge-actin interactions. At low-Ca²⁺, C-terminal domains of troponin-I (TnI) trap tropomyosin in a position on thin filaments that interferes with myosin-binding, thus causing muscle relaxation. Steric inhibition is reversed at high-Ca²⁺ when TnI releases from F-actin-tropomyosin as Ca²⁺ and the TnI switch-peptide bind to the N-lobe of troponin-C (TnC). The opposite end of cardiac TnI contains a phosphorylation-sensitive ∼30 residue-long N-terminal peptide that is absent in skeletal muscle, and likely modifies these interactions in hearts. Here, PKA-dependent phosphorylation of serine 23 and 2

SUBMITTER: Pavadai E 

PROVIDER: S-EPMC10680062 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature