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5xbf

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Revision as of 07:53, 6 December 2017

Crystal Structure of Myo7b C-terminal MyTH4-FERM in complex with USH1C PDZ3

Structural highlights

5xbf is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	MYO7B (HUMAN), USH1C, AIE75 (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

[MYO7B_HUMAN] Myosins are actin-based motor molecules with ATPase activity. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. As part of the intermicrovillar adhesion complex/IMAC plays a role in epithelial brush border differentiation, controlling microvilli organization and length. May link the complex to the actin core bundle of microvilli (Probable).^[3] ^[4] [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).

Publication Abstract from PubMed

Unconventional myosin 7a (Myo7a), myosin 7b (Myo7b), and myosin 15a (Myo15a) all contain MyTH4-FERM domains (myosin tail homology 4-band 4.1, ezrin, radixin, moesin; MF) in their cargo binding tails and are essential for the growth and function of microvilli and stereocilia. Numerous mutations have been identified in the MyTH4-FERM tandems of these myosins in patients suffering visual and hearing impairment. Although a number of MF domain binding partners have been identified, the molecular basis of interactions with the C-terminal MF domain (CMF) of these myosins remains poorly understood. Here we report the high-resolution crystal structure of Myo7b CMF in complex with the extended PDZ3 domain of USH1C (a.k.a., Harmonin), revealing a previously uncharacterized interaction mode both for MyTH4-FERM tandems and for PDZ domains. We predicted, based on the structure of the Myo7b CMF/USH1C PDZ3 complex, and verified that Myo7a CMF also binds to USH1C PDZ3 using a similar mode. The structure of the Myo7b CMF/USH1C PDZ complex provides mechanistic explanations for >20 deafness-causing mutations in Myo7a CMF. Taken together, these findings suggest that binding to PDZ domains, such as those from USH1C, PDZD7, and Whirlin, is a common property of CMFs of Myo7a, Myo7b, and Myo15a.

Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by MyTH4-FERM myosins.,Li J, He Y, Weck ML, Lu Q, Tyska MJ, Zhang M Proc Natl Acad Sci U S A. 2017 May 9;114(19):E3776-E3785. doi:, 10.1073/pnas.1702251114. Epub 2017 Apr 24. PMID:28439001^[5]

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
↑ Crawley SW, Shifrin DA Jr, Grega-Larson NE, McConnell RE, Benesh AE, Mao S, Zheng Y, Zheng QY, Nam KT, Millis BA, Kachar B, Tyska MJ. Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion. Cell. 2014 Apr 10;157(2):433-46. doi: 10.1016/j.cell.2014.01.067. PMID:24725409 doi:http://dx.doi.org/10.1016/j.cell.2014.01.067
↑ Crawley SW, Weck ML, Grega-Larson NE, Shifrin DA Jr, Tyska MJ. ANKS4B Is Essential for Intermicrovillar Adhesion Complex Formation. Dev Cell. 2016 Jan 25;36(2):190-200. doi: 10.1016/j.devcel.2015.12.022. PMID:26812018 doi:http://dx.doi.org/10.1016/j.devcel.2015.12.022
↑ Li J, He Y, Weck ML, Lu Q, Tyska MJ, Zhang M. Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by MyTH4-FERM myosins. Proc Natl Acad Sci U S A. 2017 May 9;114(19):E3776-E3785. doi:, 10.1073/pnas.1702251114. Epub 2017 Apr 24. PMID:28439001 doi:http://dx.doi.org/10.1073/pnas.1702251114

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5xbf"

@@ Line 3: / Line 3: @@
 <StructureSection load='5xbf' size='340' side='right' caption='[[5xbf]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5xbf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XBF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XBF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xbf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XBF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XBF FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MYO7B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), USH1C, AIE75 ([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=5xbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xbf OCA], [http://pdbe.org/5xbf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xbf RCSB], [http://www.ebi.ac.uk/pdbsum/5xbf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xbf ProSAT]</span></td></tr>
 </table>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: He, Y]]
 [[Category: Li, J]]

5xbf

From Proteopedia

Revision as of 07:53, 6 December 2017

Crystal Structure of Myo7b C-terminal MyTH4-FERM in complex with USH1C PDZ3

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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