| Structural highlights
5wsv is a 4 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 5wst, 5wsu |
| Gene: | CALM1, CALM, CAM, CAM1, CALM2, CAM2, CAMB, CALM3, CALML2, CAM3, CAMC, CAMIII (HUMAN), Myo7a, Myo7 (LK3 transgenic mice) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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 PubMed
Several 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
- ↑ Gibson F, Walsh J, Mburu P, Varela A, Brown KA, Antonio M, Beisel KW, Steel KP, Brown SD. A type VII myosin encoded by the mouse deafness gene shaker-1. Nature. 1995 Mar 2;374(6517):62-4. PMID:7870172 doi:http://dx.doi.org/10.1038/374062a0
- ↑ Lopes VS, Gibbs D, Libby RT, Aleman TS, Welch DL, Lillo C, Jacobson SG, Radu RA, Steel KP, Williams DS. The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65. Hum Mol Genet. 2011 Jul 1;20(13):2560-70. doi: 10.1093/hmg/ddr155. Epub 2011 Apr , 14. PMID:21493626 doi:http://dx.doi.org/10.1093/hmg/ddr155
- ↑ Grati M, Kachar B. Myosin VIIa and sans localization at stereocilia upper tip-link density implicates these Usher syndrome proteins in mechanotransduction. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11476-81. doi:, 10.1073/pnas.1104161108. Epub 2011 Jun 27. PMID:21709241 doi:10.1073/pnas.1104161108
- ↑ Li J, Chen Y, Deng Y, Unarta IC, Lu Q, Huang X, Zhang M. Ca2+-Induced Rigidity Change of the Myosin VIIa IQ Motif-Single alpha Helix Lever Arm Extension. Structure. 2017 Apr 4;25(4):579-591.e4. doi: 10.1016/j.str.2017.02.002. Epub 2017, Mar 2. PMID:28262393 doi:http://dx.doi.org/10.1016/j.str.2017.02.002
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