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TitlePseudo-acetylation of ACTC1 K326 and K328 promotes dysinhibition of reconstituted human cardiac thin filaments.
Journal, issue, pagesJ Mol Cell Cardiol, Vol. 212, Page 10-15, Year 2025
Publish dateDec 22, 2025
AuthorsKripa Chitre / Olga E Karpicheva / Chloe J King / Michael J Rynkiewicz / Axel J Fenwick / John F Dawson / D Brian Foster / William Lehman / Anthony Cammarato /
PubMed AbstractElectrostatic interactions between actin residues K326 and K328 and tropomyosin bias tropomyosin to an F-actin location where it blocks myosin attachment. K326/328 acetylation neutralizes their ...Electrostatic interactions between actin residues K326 and K328 and tropomyosin bias tropomyosin to an F-actin location where it blocks myosin attachment. K326/328 acetylation neutralizes their charge, potentially disrupting thin filament-based contractile regulation. We verified acetylation of K326/328 on human cardiac actin (ACTC1) and generated recombinant K326/328Q, pseudo-acetylated ACTC1. Pseudo-acetylation reduced inhibition of myosin-driven motility of F-actin-tropomyosin and F-actin-tropomyosin-troponin at low Ca. Cryo-EM-based and computational modeling revealed that pseudo-acetylation did not alter tropomyosin positioning along F-actin but decreased local F-actin-tropomyosin interaction energy. Thus, by reducing the energetic demands required for myosin to displace tropomyosin, ACTC1 K326/328 acetylation may promote contractile activation.
External linksJ Mol Cell Cardiol / PubMed:41443503
MethodsEM (helical sym.)
Resolution2.79 - 3.12 Å
Structure data

EMDB-73993, PDB-9zbl:
Helical Reconstruction of the Human Cardiac F-Actin-Tropomyosin Complex
Method: EM (helical sym.) / Resolution: 2.79 Å

EMDB-73996, PDB-9zbp:
Helical Reconstruction of the Complex of Pseudo-Acetylated Human Cardiac Actin (K326/328Q) and Tropomyosin
Method: EM (helical sym.) / Resolution: 3.12 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
KeywordsMOTOR PROTEIN / F-actin / tropomyosin / muscle / cryo-EM structure / motor proteins / Lysine acetylation / steric regulation

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