The tail binds to the head-neck domain, inhibiting ATPase activity of myosin VIIA
Department of Physiology; Department of Cell Biology; Program in Molecular Medicine
Animals; Drosophila melanogaster; Dyneins; Enzyme Activation; Motor Activity; Myosins; Protein Binding
Life Sciences | Medicine and Health Sciences
Myosin VIIA is an unconventional myosin, responsible for human Usher syndrome type 1B, which causes hearing and visual loss. Here, we studied the molecular mechanism of regulation of myosin VIIA, which is currently unknown. Although it was originally thought that myosin VIIA is a dimeric myosin, our electron microscopic (EM) observations revealed that full-length Drosophila myosin VIIA (DM7A) is a monomer. Interestingly, the tail domain markedly inhibits the actin-activated ATPase activity of tailless DM7A at low Ca(2+) but not high Ca(2+). By examining various deletion constructs, we found that deletion of the distal IQ domain, the C-terminal region of the tail, and the N-terminal region of the tail abolishes the tail-induced inhibition of ATPase activity. Single-particle EM analysis of full-length DM7A at low Ca(2+) suggests that the tail folds back on to the head, where it contacts both the motor core domain and the neck domain, forming an inhibited conformation. We concluded that unconventional myosin that may be present a monomer in the cell can be regulated by intramolecular interaction of the tail with the head.
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Citation: Proc Natl Acad Sci U S A. 2009 May 26;106(21):8483-8. Epub 2009 May 7. Link to article on publisher's site