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TitleThe structure of the native cardiac crossbridge in the rigor state.
Journal, issue, pagesSci Adv, Vol. 12, Issue 35, Page eaeg1209, Year 2026
Publish dateAug 28, 2026
AuthorsCristina M Risi / Tyler Nguyen / Betty Belknap / Howard D White / Jose R Pinto / Prescott B Chase / Vitold E Galkin /
PubMed AbstractCardiac 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 ...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.
External linksSci Adv / PubMed:42647613 / PubMed Central
MethodsEM (single particle)
Resolution4.32 - 5.3 Å
Structure data

72724

9ya8

EMDB-72724, PDB-9ya8:
The structure of the cardiac native crossbridge in the rigor state, myosin heads bound to actin molecules 6 and 7
Method: EM (single particle) / Resolution: 4.32 Å

72734

9yaq

EMDB-72734, PDB-9yaq:
The structure of the cardiac native cross bridge in the rigor state, myosin heads bound to actin molecules 5 and 6.
Method: EM (single particle) / Resolution: 4.63 Å

73030

9yjp

EMDB-73030, PDB-9yjp:
The structure of the cardiac native crossbridge in the rigor state, myosin heads bound to actin molecules 2 and 3
Method: EM (single particle) / Resolution: 4.8 Å

73042

9yk9

EMDB-73042, PDB-9yk9:
The structure of the cardiac native crossbridge in the rigor state, myosin heads bound to actin molecules 1 and 2
Method: EM (single particle) / Resolution: 4.5 Å

73055

9ykn

EMDB-73055, PDB-9ykn:
The structure of the cardiac native crossbridge in the rigor state, myosin heads with essential and regulatory light chains bound to actin molecules 6 and 7
Method: EM (single particle) / Resolution: 5.3 Å

Chemicals

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

ChemComp-MG:
Unknown entry

ChemComp-CA:
Unknown entry

Source
  • sus scrofa (pig)
KeywordsMOTOR PROTEIN / cardiac myosin / tropomyosin / thin filament / troponin

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