Revisiting the SRX paradox for myosin and myofibrils

Mant-ATP displacement assays in isolated myosin from multiple sources show no slow component, providing no evidence for the biochemically-defined SRX state in monomeric myosin or synthetic filaments.

• Why it matters: The SRX paradox challenges whether the super relaxed state exists outside specific biochemical definitions, and whether it can persist when myosin heads must be thermally equilibrated with DRX.
• What they did: The assay was repeated for isolated monomeric myosin and synthetic myosin filaments, using the original mant-ATP displacement approach, and tested further with Mavacamten or 2'-deoxyATP (dATP) to probe head–head interactions.
• The result: In isolated myosin, any IHM is linked to rapid equilibrium with DRX heads, while myofibril assays reveal two displacement components, consistent with distinct sarcomere thick-filament myosin populations with different IHM fractions.

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