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| Title | Pseudo-acetylation of ACTC1 K326 and K328 promotes dysinhibition of reconstituted human cardiac thin filaments. |
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| Journal, issue, pages | J Mol Cell Cardiol, Vol. 212, Page 10-15, Year 2025 |
| Publish date | Dec 22, 2025 |
Authors | Kripa Chitre / Olga E Karpicheva / Chloe J King / Michael J Rynkiewicz / Axel J Fenwick / John F Dawson / D Brian Foster / William Lehman / Anthony Cammarato / ![]() |
| PubMed Abstract | 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 ...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 links | J Mol Cell Cardiol / PubMed:41443503 |
| Methods | EM (helical sym.) |
| Resolution | 2.79 - 3.12 Å |
| Structure data | EMDB-73993, PDB-9zbl: EMDB-73996, PDB-9zbp: |
| Chemicals | ![]() ChemComp-ADP: ![]() ChemComp-MG: |
| Source |
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Keywords | MOTOR PROTEIN / F-actin / tropomyosin / muscle / cryo-EM structure / motor proteins / Lysine acetylation / steric regulation |
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homo sapiens (human)
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