9ZBP

Helical Reconstruction of the Complex of Pseudo-Acetylated Human Cardiac Actin (K326/328Q) and Tropomyosin

Summary for 9ZBP

• Entry DOI: 10.2210/pdb9zbp/pdb
• Related: 9ZBL
• EMDB information: 73996
• Descriptor: Actin, alpha cardiac muscle 1, Tropomyosin alpha-1 chain, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: lysine acetylation, f-actin, tropomyosin, muscle, steric regulation, cryo-em structure, motor proteins, motor protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 386772.86

Authors

Karpicheva, O.,Rynkiewicz, M.J.,Lehman, W.,Cammarato, A. (deposition date: 2025-11-21, release date: 2026-01-14)

Primary citation

Chitre, K.,Karpicheva, O.E.,King, C.J.,Rynkiewicz, M.J.,Fenwick, A.J.,Dawson, J.F.,Foster, D.B.,Lehman, W.,Cammarato, A.
Pseudo-acetylation of ACTC1 K326 and K328 promotes dysinhibition of reconstituted human cardiac thin filaments.
J.Mol.Cell.Cardiol., 212:10-15, 2025

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 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.

PubMed: 41443503
DOI: 10.1016/j.yjmcc.2025.12.008

Experimental method

ELECTRON MICROSCOPY (3.12 Å)