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2kbq

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Revision as of 10:13, 18 July 2018

Solution structure of harmonin N terminal domain

Structural highlights

2kbq is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2kbr, 2kbs
Gene:	HARMONIN (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2kbq"

@@ Line 1: / Line 1: @@
 ==Solution structure of harmonin N terminal domain==
 <StructureSection load='2kbq' size='340' side='right' caption='[[2kbq]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2kbr|2kbr]], [[2kbs|2kbs]]</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='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]</span></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>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kb/2kbq_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kb/2kbq_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 30: / Line 31: @@
 </div>
 <div class="pdbe-citations 2kbq" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Harmonin|Harmonin]]
 == References ==
 <references/>
@@ Line 39: / Line 43: @@
 [[Category: Yan, J]]
 [[Category: Zhang, M]]
+[[Category: Alternative splicing]]
+[[Category: Coiled coil]]
 [[Category: Deafness]]
 [[Category: Hearing]]
 [[Category: Non-syndromic deafness]]
+[[Category: Polymorphism]]
 [[Category: Protein]]
 [[Category: Retinitis pigmentosa]]

2kbq

From Proteopedia

Revision as of 10:13, 18 July 2018

Solution structure of harmonin N terminal domain

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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