The myosin interacting-heads motif present in live tarantula muscle explains tetanic and posttetanic phosphorylation mechanisms
Craig, Roger W.
UMass Chan AffiliationsCraig Lab
Division of Cell Biology and Imaging, Department of Radiology
Document TypeJournal Article
Keywordsmyosin interacting-heads motif
thick filament activation
Amino Acids, Peptides, and Proteins
Cellular and Molecular Physiology
Enzymes and Coenzymes
Musculoskeletal, Neural, and Ocular Physiology
MetadataShow full item record
AbstractStriated 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.
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