The Structure of the Native Cardiac Crossbridge in the Rigor State

Authors

• Cristina M. Risi, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Tyler Nguyen, Macon & Joan Brock Virginia Health Sciences at Old Dominion University
• Betty Belknap, Macon & Joan Brock Virginia Health Sciences at Old Dominion University
• Howard D. White, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Jose R. Pinto, Florida State University
• Prescott B. Chase, Florida State University
• Vitold E. Galkin, Macon & Joan Brock Virginia Health Sciences at Old Domionion UniversityFollow

ORCID

0000-0002-3145-2072 (Risi), 0000-0002-0935-0336 (Belknap)

Document Type

Article

Publication Date

2026

DOI

10.1126/sciadv.aeg1209

Publication Title

Science Advances

Volume

12

Issue

35

Pages

eaeg1209 (15 pp.)

Abstract

Cardiac contraction is driven by double-headed myosin cycling on cardiac thin filaments, where troponin-tropomyosin regulates myosin access to actin. Prior high-resolution structural studies used a single-headed myosin bound to bare actin, thereby limiting insight into coordination between myosin heads and the influence of troponin-tropomyosin on actomyosin interactions. Here, we report a high-resolution structure of the native cardiac rigor cross-bridge formed by heavy meromyosin bound to the thin filament. We show that direct communication between the two bound heads, uneven interactions between the heads and tropomyosin, and spatial constraints imposed by troponin govern myosin placement along the thin filament. Additionally, the two heads display non-equivalent motor-light chain interactions, yielding distinct lever-arm conformations indicative of asymmetric intramolecular strain. Together, these findings provide a structural framework for how the two myosin heads coordinate and how the components of the thin filament are integrated into force generation by active cross-bridges.

Rights

© 2026 The Authors, some rights reserved.

Distributed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Data Availability

Article states: "This study did not generate new materials. All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Atomic models and associated electron density maps are available from the RCSB PDB repository (https://www.rcsb.org/) using the following accession numbers: PDB: 9YA8, 9YAQ, 9YJP, 9YK9, 9YKN, while density maps can be downloaded from the Electron Microscopy Data Bank (https://www.emdataresource.org/) with the following accession numbers: EMD: 72724, 72734, 73030, 73042, 73055."

Original Publication Citation

Risi, C. M., Nguyen, T., Belknap, B., White, H. D., Pinto, J. R., Chase, P. B., & Galkin, V. E. (2026). The structure of the native cardiac crossbridge in the rigor state. Science Advances, 12(35), Article eaeg1209. https://doi.org/10.1126/sciadv.aeg1209

Repository Citation

Risi, C. M., Nguyen, T., Belknap, B., White, H. D., Pinto, J. R., Chase, P. B., & Galkin, V. E. (2026). The structure of the native cardiac crossbridge in the rigor state. Science Advances, 12(35), Article eaeg1209. https://doi.org/10.1126/sciadv.aeg1209