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| | <StructureSection load='3pvl' size='340' side='right'caption='[[3pvl]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='3pvl' size='340' side='right'caption='[[3pvl]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3pvl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PVL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PVL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3pvl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PVL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PVL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Myo7a ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), USH1G, SANS ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3pvl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pvl OCA], [https://pdbe.org/3pvl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pvl RCSB], [https://www.ebi.ac.uk/pdbsum/3pvl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pvl ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3pvl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pvl OCA], [https://pdbe.org/3pvl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pvl RCSB], [https://www.ebi.ac.uk/pdbsum/3pvl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pvl ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/MYO7A_MOUSE 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.<ref>PMID:7870172</ref> [[https://www.uniprot.org/uniprot/USH1G_HUMAN USH1G_HUMAN]] Defects in USH1G are the cause of Usher syndrome type 1G (USH1G) [MIM:[https://omim.org/entry/606943 606943]]. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa and sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness.<ref>PMID:21709241</ref> <ref>PMID:12588794</ref> <ref>PMID:20142502</ref> <ref>PMID:16283141</ref>
| + | [https://www.uniprot.org/uniprot/MYO7A_MOUSE 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.<ref>PMID:7870172</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/MYO7A_MOUSE 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.<ref>PMID:21493626</ref> <ref>PMID:21709241</ref> [[https://www.uniprot.org/uniprot/USH1G_HUMAN USH1G_HUMAN]] Required for normal development and maintenance of cochlear hair cell bundles. Anchoring/scaffolding 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.<ref>PMID:21709241</ref> <ref>PMID:12588794</ref>
| + | [https://www.uniprot.org/uniprot/MYO7A_MOUSE 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.<ref>PMID:21493626</ref> <ref>PMID:21709241</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The unconventional myosin VIIa (MYO7A) is one of the five proteins that form a network of complexes involved in formation of stereocilia. Defects in these proteins cause syndromic deaf-blindness in humans [Usher syndrome I (USH1)]. Many disease-causing mutations occur in myosin tail homology 4-protein 4.1, ezrin, radixin, moesin (MyTH4-FERM) domains in the myosin tail that binds to another USH1 protein, Sans. We report the crystal structure of MYO7A MyTH4-FERM domains in complex with the central domain (CEN) of Sans at 2.8 angstrom resolution. The MyTH4 and FERM domains form an integral structural and functional supramodule binding to two highly conserved segments (CEN1 and 2) of Sans. The MyTH4-FERM/CEN complex structure provides mechanistic explanations for known deafness-causing mutations in MYO7A MyTH4-FERM. The structure will also facilitate mechanistic and functional studies of MyTH4-FERM domains in other myosins.
| + | |
| - | | + | |
| - | Structure of MyTH4-FERM domains in myosin VIIa tail bound to cargo.,Wu L, Pan L, Wei Z, Zhang M Science. 2011 Feb 11;331(6018):757-60. PMID:21311020<ref>PMID:21311020</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3pvl" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Pan, L F]] | + | [[Category: Pan LF]] |
| - | [[Category: Wei, Z Y]] | + | [[Category: Wei ZY]] |
| - | [[Category: Wu, L]] | + | [[Category: Wu L]] |
| - | [[Category: Zhang, M J]] | + | [[Category: Zhang MJ]] |
| - | [[Category: Cargo protein]]
| + | |
| - | [[Category: Motor protein-protein transport complex]]
| + | |
| - | [[Category: Novel folding]]
| + | |
| - | [[Category: Protein cargo binding]]
| + | |
| - | [[Category: Protein complex]]
| + | |
| 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]
See Also
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
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