Department of Cell and Developmental Biology; Department of Radiology; Craig Lab
Biochemistry | Cell Biology | Cellular and Molecular Physiology
Electron microscope studies have shown that the switched-off state of myosin II in muscle involves intramolecular interaction between the two heads of myosin and between one head and the tail. The interaction, seen in both myosin filaments and isolated molecules, inhibits activity by blocking actin-binding and ATPase sites on myosin. This interacting-heads motif is highly conserved, occurring in invertebrates and vertebrates, in striated, smooth, and nonmuscle myosin IIs, and in myosins regulated by both Ca(2+) binding and regulatory light-chain phosphorylation. Our goal was to determine how early this motif arose by studying the structure of inhibited myosin II molecules from primitive animals and from earlier, unicellular species that predate animals. Myosin II from Cnidaria (sea anemones, jellyfish), the most primitive animals with muscles, and Porifera (sponges), the most primitive of all animals (lacking muscle tissue) showed the same interacting-heads structure as myosins from higher animals, confirming the early origin of the motif. The social amoeba Dictyostelium discoideum showed a similar, but modified, version of the motif, while the amoeba Acanthamoeba castellanii and fission yeast (Schizosaccharomyces pombe) showed no head-head interaction, consistent with the different sequences and regulatory mechanisms of these myosins compared with animal myosin IIs. Our results suggest that head-head/head-tail interactions have been conserved, with slight modifications, as a mechanism for regulating myosin II activity from the emergence of the first animals and before. The early origins of these interactions highlight their importance in generating the inhibited (relaxed) state of myosin in muscle and nonmuscle cells.
evolution, interacting-heads motif, muscle, myosin II, myosin regulation
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© 2018. Published under the PNAS license, http://www.pnas.org/page/authors/licenses.
DOI of Published Version
Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):E1991-E2000. doi: 10.1073/pnas.1715247115. Epub 2018 Feb 14. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Lee K, Sulbaran G, Yang S, Mun J, Alamo L, Pinto A, Sato O, Ikebe M, Liu X, Korn ED, Sarsoza F, Bernstein SI, Padron R, Craig R. (2018). Interacting-heads motif has been conserved as a mechanism of myosin II inhibition since before the origin of animals. Radiology Publications and Presentations. https://doi.org/10.1073/pnas.1715247115. Retrieved from https://escholarship.umassmed.edu/radiology_pubs/379