View source for 5mv9


==Structure of human Myosin 7a C-terminal MyTH4-FERM domain in complex with harmonin-a PDZ3 domain==
<StructureSection load='5mv9' size='340' side='right'caption='[[5mv9]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mv9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MV9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MV9 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=5mv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mv9 OCA], [https://pdbe.org/5mv9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mv9 RCSB], [https://www.ebi.ac.uk/pdbsum/5mv9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mv9 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MYO7A_HUMAN MYO7A_HUMAN] Autosomal dominant non-syndromic sensorineural deafness type DFNA;Autosomal recessive non-syndromic sensorineural deafness type DFNB;Usher syndrome type 1;Usher syndrome type 2. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/MYO7A_HUMAN MYO7A_HUMAN] 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. In the inner ear, plays an important role in differentiation, morphogenesis and organization of cochlear hair cell bundles. Involved in hair-cell vesicle trafficking of aminoglycosides, which are known to induce ototoxicity (By similarity). 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.<ref>PMID:19643958</ref> <ref>PMID:21493626</ref> <ref>PMID:21687988</ref> <ref>PMID:21709241</ref> 
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== Publication Abstract from PubMed ==
Cadherin linkages between adjacent stereocilia and microvilli are essential for mechanotransduction and maintaining their organization. They are anchored to actin through interaction of their cytoplasmic domains with related tripartite complexes consisting of a class VII myosin and adaptor proteins: Myo7a/SANS/Harmonin in stereocilia and Myo7b/ANKS4B/Harmonin in microvilli. Here, we determine high-resolution structures of Myo7a and Myo7b C-terminal MyTH4-FERM domain (MF2) and unveil how they recognize harmonin using a novel binding mode. Systematic definition of interactions between domains of the tripartite complex elucidates how the complex assembles and prevents possible self-association of harmonin-a. Several Myo7a deafness mutants that map to the surface of MF2 disrupt harmonin binding, revealing the molecular basis for how they impact the formation of the tripartite complex and disrupt mechanotransduction. Our results also suggest how switching between different harmonin isoforms can regulate the formation of networks with Myo7a motors and coordinate force sensing in stereocilia.

Myosin 7 and its adaptors link cadherins to actin.,Yu IM, Planelles-Herrero VJ, Sourigues Y, Moussaoui D, Sirkia H, Kikuti C, Stroebel D, Titus MA, Houdusse A Nat Commun. 2017 Jun 29;8:15864. doi: 10.1038/ncomms15864. PMID:28660889<ref>PMID:28660889</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5mv9" style="background-color:#fffaf0;"></div>

==See Also==
*[[Harmonin|Harmonin]]
*[[Myosin 3D Structures|Myosin 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Houdusse A]]
[[Category: Sourigues Y]]
[[Category: Titus MA]]
[[Category: Yu I]]