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Speaker: Dr Charlotte Scarff, Astbury Centre for Structural Molecular Biology, University of Leeds
Host: Elisabeth Ehler
Myosin-2 is a molecular motor that is essential for cell movement, cell division and muscle contraction. In its active state, it forms filaments, interacts with actin, and uses the energy from ATP hydrolysis to generate movement. It also forms a switched-off state, conserved across myosin-2 isoforms, in which ATPase activity is very low. In smooth and non-muscle myosin-2, in this state, termed shutdown, myosin filaments are disassembled into monomers, the filament-forming tail wraps around the two heads of the monomer, with the heads bent back and interacting with one another in the so-called interacting-heads motif (IHM). This shutdown state serves as a storage state and enables diffusion. In striated muscle, in the switched-off state, the tails remain polymerised into filaments but the heads on the filament surface adopt an IHM.
In this seminar, I will present our recent work using cryo-electron microscopy to solve the structure of shutdown smooth muscle myosin, revealing how it is stabilised by multiple interaction interfaces and suggesting how phosphorylation leads to myosin activation. I will discuss how this relates to the IHM found in striated muscle and present our work on the IHM of beta-cardiac myosin, discussing its relevance to inherited heart disease.