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| | ==Solution structure of human Myosin VI isoform3 (998-1071)== | | ==Solution structure of human Myosin VI isoform3 (998-1071)== |
| - | <StructureSection load='2n11' size='340' side='right' caption='[[2n11]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2n11' size='340' side='right'caption='[[2n11]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2n11]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N11 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N11 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2n11]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N11 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N11 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2n0z|2n0z]], [[2n10|2n10]], [[2n12|2n12]], [[2n13|2n13]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2n11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n11 OCA], [http://pdbe.org/2n11 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n11 RCSB], [http://www.ebi.ac.uk/pdbsum/2n11 PDBsum]</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=2n11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n11 OCA], [https://pdbe.org/2n11 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n11 RCSB], [https://www.ebi.ac.uk/pdbsum/2n11 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n11 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/MYO6_HUMAN MYO6_HUMAN]] Autosomal dominant non-syndromic sensorineural deafness type DFNA;Autosomal recessive non-syndromic sensorineural deafness type DFNB;Progressive sensorineural hearing loss - hypertrophic cardiomyopathy. 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. | + | [https://www.uniprot.org/uniprot/MYO6_HUMAN MYO6_HUMAN] Autosomal dominant non-syndromic sensorineural deafness type DFNA;Autosomal recessive non-syndromic sensorineural deafness type DFNB;Progressive sensorineural hearing loss - hypertrophic cardiomyopathy. 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 == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MYO6_HUMAN MYO6_HUMAN]] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. May act as a regulator of F-actin dynamics. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. Required for structural integrity of inner ear hair cells (By similarity).<ref>PMID:10519557</ref> <ref>PMID:11447109</ref> <ref>PMID:16507995</ref> <ref>PMID:16949370</ref> | + | [https://www.uniprot.org/uniprot/MYO6_HUMAN MYO6_HUMAN] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. May act as a regulator of F-actin dynamics. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. Required for structural integrity of inner ear hair cells (By similarity).<ref>PMID:10519557</ref> <ref>PMID:11447109</ref> <ref>PMID:16507995</ref> <ref>PMID:16949370</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Myosin VI is critical for cargo trafficking and sorting during early endocytosis and autophagosome maturation, and abnormalities in these processes are linked to cancers, neurodegeneration, deafness, and hypertropic cardiomyopathy. We identify a structured domain in myosin VI, myosin VI ubiquitin-binding domain (MyUb), that binds to ubiquitin chains, especially those linked via K63, K11, and K29. Herein, we solve the solution structure of MyUb and MyUb:K63-linked diubiquitin. MyUb folds as a compact helix-turn-helix-like motif and nestles between the ubiquitins of K63-linked diubiquitin, interacting with distinct surfaces of each. A nine-amino-acid extension at the C-terminal helix (Helix2) of MyUb is required for myosin VI interaction with endocytic and autophagic adaptors. Structure-guided mutations revealed that a functional MyUb is necessary for optineurin interaction. In addition, we found that an isoform-specific helix restricts MyUb binding to ubiquitin chains. This work provides fundamental insights into myosin VI interaction with ubiquitinated cargo and functional adaptors.
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| - | Myosin VI Contains a Compact Structural Motif that Binds to Ubiquitin Chains.,He F, Wollscheid HP, Nowicka U, Biancospino M, Valentini E, Ehlinger A, Acconcia F, Magistrati E, Polo S, Walters KJ Cell Rep. 2016 Mar 22;14(11):2683-94. doi: 10.1016/j.celrep.2016.01.079. Epub, 2016 Mar 10. PMID:26971995<ref>PMID:26971995</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 2n11" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: He, F]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Walters, K]] | + | [[Category: Large Structures]] |
| - | [[Category: Motor protein]] | + | [[Category: He F]] |
| - | [[Category: Protein transport]] | + | [[Category: Walters K]] |
| Structural highlights
Disease
MYO6_HUMAN Autosomal dominant non-syndromic sensorineural deafness type DFNA;Autosomal recessive non-syndromic sensorineural deafness type DFNB;Progressive sensorineural hearing loss - hypertrophic cardiomyopathy. 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
MYO6_HUMAN Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. May act as a regulator of F-actin dynamics. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. Required for structural integrity of inner ear hair cells (By similarity).[1] [2] [3] [4]
References
- ↑ Wells AL, Lin AW, Chen LQ, Safer D, Cain SM, Hasson T, Carragher BO, Milligan RA, Sweeney HL. Myosin VI is an actin-based motor that moves backwards. Nature. 1999 Sep 30;401(6752):505-8. PMID:10519557 doi:http://dx.doi.org/10.1038/46835
- ↑ Buss F, Arden SD, Lindsay M, Luzio JP, Kendrick-Jones J. Myosin VI isoform localized to clathrin-coated vesicles with a role in clathrin-mediated endocytosis. EMBO J. 2001 Jul 16;20(14):3676-84. PMID:11447109 doi:http://dx.doi.org/10.1093/emboj/20.14.3676
- ↑ Jung EJ, Liu G, Zhou W, Chen X. Myosin VI is a mediator of the p53-dependent cell survival pathway. Mol Cell Biol. 2006 Mar;26(6):2175-86. PMID:16507995 doi:http://dx.doi.org/10.1128/MCB.26.6.2175-2186.2006
- ↑ Vreugde S, Ferrai C, Miluzio A, Hauben E, Marchisio PC, Crippa MP, Bussi M, Biffo S. Nuclear myosin VI enhances RNA polymerase II-dependent transcription. Mol Cell. 2006 Sep 1;23(5):749-55. PMID:16949370 doi:http://dx.doi.org/10.1016/j.molcel.2006.07.005
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