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| | ==Solution structure of harmonin N terminal domain== | | ==Solution structure of harmonin N terminal domain== |
| - | <StructureSection load='2kbq' size='340' side='right' caption='[[2kbq]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kbq' size='340' side='right'caption='[[2kbq]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kbq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KBQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KBQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kbq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KBQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KBQ FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2kbr|2kbr]], [[2kbs|2kbs]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2kbr|2kbr]], [[2kbs|2kbs]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HARMONIN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HARMONIN ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2kbq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kbq OCA], [http://pdbe.org/2kbq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kbq RCSB], [http://www.ebi.ac.uk/pdbsum/2kbq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kbq 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=2kbq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kbq OCA], [https://pdbe.org/2kbq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kbq RCSB], [https://www.ebi.ac.uk/pdbsum/2kbq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kbq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/USH1C_HUMAN USH1C_HUMAN]] Defects in USH1C are the cause of Usher syndrome type 1C (USH1C) [MIM:[http://omim.org/entry/276904 276904]]; also known as Usher syndrome type I Acadian variety. 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:10973247</ref> Defects in USH1C are the cause of deafness, autosomal recessive, 18A (DFNB18A) [MIM:[http://omim.org/entry/602092 602092]]. A form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:12107438</ref> | + | [[https://www.uniprot.org/uniprot/USH1C_HUMAN USH1C_HUMAN]] Defects in USH1C are the cause of Usher syndrome type 1C (USH1C) [MIM:[https://omim.org/entry/276904 276904]]; also known as Usher syndrome type I Acadian variety. 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:10973247</ref> Defects in USH1C are the cause of deafness, autosomal recessive, 18A (DFNB18A) [MIM:[https://omim.org/entry/602092 602092]]. A form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:12107438</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/USH1C_HUMAN USH1C_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 (By similarity). | + | [[https://www.uniprot.org/uniprot/USH1C_HUMAN USH1C_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 (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Pan, L]] | | [[Category: Pan, L]] |
| | [[Category: Wu, L]] | | [[Category: Wu, L]] |
| Structural highlights
Disease
[USH1C_HUMAN] Defects in USH1C are the cause of Usher syndrome type 1C (USH1C) [MIM:276904]; also known as Usher syndrome type I Acadian variety. 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.[1] Defects in USH1C are the cause of deafness, autosomal recessive, 18A (DFNB18A) [MIM:602092]. A form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.[2]
Function
[USH1C_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 (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The hereditary hearing-vision loss disease Usher syndrome (USH) is caused by defects in several proteins, most of which form an integrated protein network called Usher interactome. Harmonin/Ush1C is a master scaffold in the assembly of the Usher protein complexes, because harmonin is known to bind to every protein in the Usher interactome. However, the biochemical and structural mechanism governing the Usher protein complex formation is largely unclear. Here, we report that the highly-conserved N-terminal fragment of harmonin (N-domain) immediately preceding its PDZ1 adopts an autonomously-folded domain. We discovered that the N-domain specifically binds to a short internal peptide fragment of the cadherin 23 cytoplasmic domain. The structures of the harmonin N-domain alone and in complex with the cadherin 23 internal peptide fragment uncovered the detailed binding mechanism of this interaction between harmonin and cadherin 23. We further elucidated the harmonin PDZ domain-mediated cadherin 23 binding by solving the structure of the second harmonin PDZ domain in complex with the cadherin 23 carboxyl tail. The multidentate binding mode between harmonin and cadherin 23 provides a structural and biochemical basis for the harmonin-mediated assembly of stable tip link complex in the auditory hair cells.
Assembling stable hair cell tip link complex via multidentate interactions between harmonin and cadherin 23.,Pan L, Yan J, Wu L, Zhang M Proc Natl Acad Sci U S A. 2009 Mar 18. PMID:19297620[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Verpy E, Leibovici M, Zwaenepoel I, Liu XZ, Gal A, Salem N, Mansour A, Blanchard S, Kobayashi I, Keats BJ, Slim R, Petit C. A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C. Nat Genet. 2000 Sep;26(1):51-5. PMID:10973247 doi:10.1038/79171
- ↑ Ahmed ZM, Smith TN, Riazuddin S, Makishima T, Ghosh M, Bokhari S, Menon PS, Deshmukh D, Griffith AJ, Riazuddin S, Friedman TB, Wilcox ER. Nonsyndromic recessive deafness DFNB18 and Usher syndrome type IC are allelic mutations of USHIC. Hum Genet. 2002 Jun;110(6):527-31. Epub 2002 May 3. PMID:12107438 doi:10.1007/s00439-002-0732-4
- ↑ Pan L, Yan J, Wu L, Zhang M. Assembling stable hair cell tip link complex via multidentate interactions between harmonin and cadherin 23. Proc Natl Acad Sci U S A. 2009 Mar 18. PMID:19297620
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