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3sf4

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Revision as of 01:10, 5 August 2016

Crystal structure of the complex between the conserved cell polarity proteins Inscuteable and LGN

Structural highlights

3sf4 is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	LGN (HUMAN), INSC (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[GPSM2_HUMAN] Autosomal recessive nonsyndromic sensorineural deafness type DFNB;Chudley-McCullough syndrome. Chudley-McCullough syndrome (CMCS) [MIM:604213]: An autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal. Note=The disease is caused by mutations affecting the gene represented in this entry.^[1] ^[2]

Function

[GPSM2_HUMAN] Plays an important role in spindle pole orientation. Interacts and contributes to the functional activity of G(i) alpha proteins. Acts to stabilize the apical complex during neuroblast divisions.^[3] [INSC_HUMAN] May function as an adapter linking the Par3 complex to the GPSM1/GPSM2 complex. Involved in spindle orientation during mitosis it may regulate cell proliferation and differentiation in the developing nervous system. May play a role in the asymmetric division of fibroblasts and participate in the process of stratification of the squamous epithelium.^[4]

Publication Abstract from PubMed

Interaction between the mammalian cell polarity proteins mInsc (mammalian homologue of Inscuteable) and Leu-Gly-Asn repeat-enriched protein (LGN), as well as that between their respective Drosophila homologues Inscuteable and Partner of Inscuteable (Pins), plays crucial roles in mitotic spindle orientation, a process contributing to asymmetric cell division. Here, we report a crystal structure of the LGN-binding domain (LBD) of human mInsc complexed with the N-terminal tetratricopeptide repeat (TPR) motifs of human LGN at 2.6-A resolution. In the complex, mInsc-LBD adopts an elongated structure with three binding modules--an alpha-helix, an extended region, and a beta-sheet connected with a loop--that runs antiparallel to LGN along the concave surface of the superhelix formed by the TPRs. Structural analysis and structure-based mutagenesis define residues that are critical for mInsc-LGN association, and reveal that the activator of G-protein signaling 3 (AGS3)-binding protein Frmpd1 [4.1/ezrin/radixin/moesin (FERM) and PSD-95/Dlg/ZO-1 (PDZ) domain-containing protein 1] and its relative Frmpd4 interact with LGN via a region homologous to a part of mInsc-LBD, whereas nuclear mitotic apparatus protein (NuMA) and the C terminus of LGN recognize the TPR domain in a manner different from that by mInsc. mInsc binds to LGN with the highest affinity (K(D) approximately 2.4 nM) and effectively replaces the Frmpd proteins, NuMA, and the LGN C terminus, suggesting the priority of mInsc in binding to LGN. We also demonstrate, using mutant proteins, that mInsc-LGN interaction is vital for stabilization of LGN and for intracellular localization of mInsc.

Structural basis for interaction between the conserved cell polarity proteins Inscuteable and Leu-Gly-Asn repeat-enriched protein (LGN).,Yuzawa S, Kamakura S, Iwakiri Y, Hayase J, Sumimoto H Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19210-5. Epub 2011 Nov 10. PMID:22074847^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Walsh T, Shahin H, Elkan-Miller T, Lee MK, Thornton AM, Roeb W, Abu Rayyan A, Loulus S, Avraham KB, King MC, Kanaan M. Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82. Am J Hum Genet. 2010 Jul 9;87(1):90-4. doi: 10.1016/j.ajhg.2010.05.010. Epub 2010, Jun 17. PMID:20602914 doi:10.1016/j.ajhg.2010.05.010
↑ Doherty D, Chudley AE, Coghlan G, Ishak GE, Innes AM, Lemire EG, Rogers RC, Mhanni AA, Phelps IG, Jones SJ, Zhan SH, Fejes AP, Shahin H, Kanaan M, Akay H, Tekin M, Triggs-Raine B, Zelinski T. GPSM2 mutations cause the brain malformations and hearing loss in Chudley-McCullough syndrome. Am J Hum Genet. 2012 Jun 8;90(6):1088-93. doi: 10.1016/j.ajhg.2012.04.008. Epub, 2012 May 10. PMID:22578326 doi:10.1016/j.ajhg.2012.04.008
↑ Yasumi M, Sakisaka T, Hoshino T, Kimura T, Sakamoto Y, Yamanaka T, Ohno S, Takai Y. Direct binding of Lgl2 to LGN during mitosis and its requirement for normal cell division. J Biol Chem. 2005 Feb 25;280(8):6761-5. Epub 2005 Jan 4. PMID:15632202 doi:C400440200
↑ Izaki T, Kamakura S, Kohjima M, Sumimoto H. Two forms of human Inscuteable-related protein that links Par3 to the Pins homologues LGN and AGS3. Biochem Biophys Res Commun. 2006 Mar 24;341(4):1001-6. Epub 2006 Jan 24. PMID:16458856 doi:S0006-291X(06)00112-4
↑ Yuzawa S, Kamakura S, Iwakiri Y, Hayase J, Sumimoto H. Structural basis for interaction between the conserved cell polarity proteins Inscuteable and Leu-Gly-Asn repeat-enriched protein (LGN). Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19210-5. Epub 2011 Nov 10. PMID:22074847 doi:10.1073/pnas.1110951108

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/3sf4"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the complex between the conserved cell polarity proteins Inscuteable and LGN==
 <StructureSection load='3sf4' size='340' side='right' caption='[[3sf4]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3sf4]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SF4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SF4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3sf4]] is a 6 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=3SF4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SF4 FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LGN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), INSC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LGN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), INSC ([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=3sf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sf4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sf4 RCSB], [http://www.ebi.ac.uk/pdbsum/3sf4 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=3sf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sf4 OCA], [http://pdbe.org/3sf4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sf4 RCSB], [http://www.ebi.ac.uk/pdbsum/3sf4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sf4 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3sf4" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Hayase, J]]
 [[Category: Iwakiri, Y]]

3sf4

From Proteopedia

Revision as of 01:10, 5 August 2016

Crystal structure of the complex between the conserved cell polarity proteins Inscuteable and LGN

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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