Division of Cell Biology and Imaging, Department of Radiology; Craig Lab
Amino Acids, Peptides, and Proteins | Cellular and Molecular Physiology | Enzymes and Coenzymes | Musculoskeletal, Neural, and Ocular Physiology
Striated muscle contraction involves sliding of actin thin filaments along myosin thick filaments, controlled by calcium through thin filament activation. In relaxed muscle, the two heads of myosin interact with each other on the filament surface to form the interacting-heads motif (IHM). A key question is how both heads are released from the surface to approach actin and produce force. We used time-resolved synchrotron X-ray diffraction to study tarantula muscle before and after tetani. The patterns showed that the IHM is present in live relaxed muscle. Tetanic contraction produced only a very small backbone elongation, implying that mechanosensing-proposed in vertebrate muscle-is not of primary importance in tarantula. Rather, thick filament activation results from increases in myosin phosphorylation that release a fraction of heads to produce force, with the remainder staying in the ordered IHM configuration. After the tetanus, the released heads slowly recover toward the resting, helically ordered state. During this time the released heads remain close to actin and can quickly rebind, enhancing the force produced by posttetanic twitches, structurally explaining posttetanic potentiation. Taken together, these results suggest that, in addition to stretch activation in insects, two other mechanisms for thick filament activation have evolved to disrupt the interactions that establish the relaxed helices of IHMs: one in invertebrates, by either regulatory light-chain phosphorylation (as in arthropods) or Ca(2+)-binding (in mollusks, lacking phosphorylation), and another in vertebrates, by mechanosensing.
myosin interacting-heads motif, phosphorylation, posttetanic potentiation, skeletal muscle, thick filament activation
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© 2020. PDF posted with 6-month embargo to author's website as allowed by publisher's default license at https://www.pnas.org/page/authors/licenses.
DOI of Published Version
Padrón R, Ma W, Duno-Miranda S, Koubassova N, Lee KH, Pinto A, Alamo L, Bolaños P, Tsaturyan A, Irving T, Craig R. The myosin interacting-heads motif present in live tarantula muscle explains tetanic and posttetanic phosphorylation mechanisms. Proc Natl Acad Sci U S A. 2020 Jun 2;117(22):11865-11874. doi: 10.1073/pnas.1921312117. Epub 2020 May 22. PMID: 32444484; PMCID: PMC7275770. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Padron R, Ma W, Duno-Miranda S, Koubassova N, Lee K, Pinto A, Alamo L, Bolanos P, Tsaturyan A, Irving T, Craig RW. (2020). The myosin interacting-heads motif present in live tarantula muscle explains tetanic and posttetanic phosphorylation mechanisms. Radiology Publications. https://doi.org/10.1073/pnas.1921312117. Retrieved from https://escholarship.umassmed.edu/radiology_pubs/549
Available for download on Wednesday, December 02, 2020