5wsv
From Proteopedia
Crystal structure of Myosin VIIa IQ5 in complex with Ca2+-CaM
Structural highlights
Disease[MYO7A_MOUSE] Defects in Myo7a are the cause of the shaker-1 (sh-1) phenotype which affects only the inner ear. Sh-1 homozygote mutants show hyperactivity, head tossing and circling due to vestibular dysfunction, together with typical neuroepithelial-type cochlear defects involving dysfunction and progressive degeneration of the organ of Corti.[1] Function[MYO7A_MOUSE] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails bind to membranous compartments, which are then moved relative to actin filaments. In the retina, plays an important role in the renewal of the outer photoreceptor disks. Plays an important role in the distribution and migration of retinal pigment epithelial (RPE) melanosomes and phagosomes, and in the regulation of opsin transport in retinal photoreceptors. Mediates intracellular transport of RPE65 in the retina pigment epithelium. In the inner ear, plays an important role in differentiation, morphogenesis and organization of cochlear hair cell bundles. Motor protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal hearing. Involved in hair-cell vesicle trafficking of aminoglycosides, which are known to induce ototoxicity.[2] [3] Publication Abstract from PubMedSeveral unconventional myosins contain a highly charged single alpha helix (SAH) immediately following the calmodulin (CaM) binding IQ motifs, functioning to extend lever arms of these myosins. How such SAH is connected to the IQ motifs and whether the conformation of the IQ motifs-SAH segments are regulated by Ca2+ fluctuations are not known. Here, we demonstrate by solving its crystal structure that the predicted SAH of myosin VIIa (Myo7a) forms a stable SAH. The structure of Myo7a IQ5-SAH segment in complex with apo-CaM reveals that the SAH sequence can extend the length of the Myo7a lever arm. Although Ca2+-CaM remains bound to IQ5-SAH, the Ca2+-induced CaM binding mode change softens the conformation of the IQ5-SAH junction, revealing a Ca2+-induced lever arm flexibility change for Myo7a. We further demonstrate that the last IQ motif of several other myosins also binds to both apo- and Ca2+-CaM, suggesting a common Ca2+-induced conformational regulation mechanism. Ca2+-Induced Rigidity Change of the Myosin VIIa IQ Motif-Single alpha Helix Lever Arm Extension.,Li J, Chen Y, Deng Y, Unarta IC, Lu Q, Huang X, Zhang M Structure. 2017 Apr 4;25(4):579-591.e4. doi: 10.1016/j.str.2017.02.002. Epub 2017, Mar 2. PMID:28262393[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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