4wnd

From Proteopedia

(Difference between revisions)

Revision as of 16:58, 16 November 2017

Crystal structure of the TPR domain of LGN in complex with Frmpd4/Preso1 at 1.5 Angstrom resolution

Structural highlights

4wnd 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:	, , ,
Related:	3sf4, 4wne, 4wnf, 4wng
Gene:	GPSM2, LGN (HUMAN), FRMPD4, KIAA0316, PDZD10, PDZK10 (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] [FRPD4_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.

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] [FRPD4_HUMAN] Positive regulator of dendritic spine morphogenesis and density. Required for the maintenance of excitatory synaptic transmission. Binds phosphatidylinositol 4,5-bisphosphate.^[4]

Publication Abstract from PubMed

The adaptor protein LGN interacts via the N-terminal domain comprising eight tetratricopeptide-repeat (TPR) motifs with its partner proteins mInsc, NuMA, Frmpd1 and Frmpd4 in a mutually exclusive manner. Here, the crystal structure of the LGN TPR domain in complex with human Frmpd4 is described at 1.5 A resolution. In the complex, the LGN-binding region of Frmpd4 (amino-acid residues 990-1011) adopts an extended structure that runs antiparallel to LGN along the concave surface of the superhelix formed by the TPR motifs. Comparison with the previously determined structures of the LGN-Frmpd1, LGN-mInsc and LGN-NuMA complexes reveals that these partner proteins interact with LGN TPR1-6 via a common core binding region with consensus sequence (E/Q)XEX4-5(E/D/Q)X1-2(K/R)X0-1(V/I). In contrast to Frmpd1, Frmpd4 makes additional contacts with LGN via regions N- and C-terminal to the core sequence. The N-terminal extension is replaced by a specific alpha-helix in mInsc, which drastically increases the direct contacts with LGN TPR7/8, consistent with the higher affinity of mInsc for LGN. A crystal structure of Frmpd4-bound LGN in an oxidized form is also reported, although oxidation does not appear to strongly affect the interaction with Frmpd4.

Structural basis for the recognition of the scaffold protein Frmpd4/Preso1 by the TPR domain of the adaptor protein LGN.,Takayanagi H, Yuzawa S, Sumimoto H Acta Crystallogr F Struct Biol Commun. 2015 Feb;71(Pt 2):175-83. doi:, 10.1107/S2053230X14028143. Epub 2015 Jan 28. PMID:25664792^[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
↑ Lee HW, Choi J, Shin H, Kim K, Yang J, Na M, Choi SY, Kang GB, Eom SH, Kim H, Kim E. Preso, a novel PSD-95-interacting FERM and PDZ domain protein that regulates dendritic spine morphogenesis. J Neurosci. 2008 Dec 31;28(53):14546-56. doi: 10.1523/JNEUROSCI.3112-08.2008. PMID:19118189 doi:http://dx.doi.org/10.1523/JNEUROSCI.3112-08.2008
↑ Takayanagi H, Yuzawa S, Sumimoto H. Structural basis for the recognition of the scaffold protein Frmpd4/Preso1 by the TPR domain of the adaptor protein LGN. Acta Crystallogr F Struct Biol Commun. 2015 Feb;71(Pt 2):175-83. doi:, 10.1107/S2053230X14028143. Epub 2015 Jan 28. PMID:25664792 doi:http://dx.doi.org/10.1107/S2053230X14028143

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/4wnd"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 4wnd is ON HOLD  until Paper Publication
+==Crystal structure of the TPR domain of LGN in complex with Frmpd4/Preso1 at 1.5 Angstrom resolution==
+<StructureSection load='4wnd' size='340' side='right' caption='[[4wnd]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4wnd]] 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=4WND OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WND FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sf4|3sf4]], [[4wne|4wne]], [[4wnf|4wnf]], [[4wng|4wng]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GPSM2, LGN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FRMPD4, KIAA0316, PDZD10, PDZK10 ([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=4wnd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wnd OCA], [http://pdbe.org/4wnd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wnd RCSB], [http://www.ebi.ac.uk/pdbsum/4wnd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wnd ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/GPSM2_HUMAN GPSM2_HUMAN]] Autosomal recessive nonsyndromic sensorineural deafness type DFNB;Chudley-McCullough syndrome. Chudley-McCullough syndrome (CMCS) [MIM:[http://omim.org/entry/604213 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.<ref>PMID:20602914</ref> <ref>PMID:22578326</ref>  [[http://www.uniprot.org/uniprot/FRPD4_HUMAN FRPD4_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[[http://www.uniprot.org/uniprot/GPSM2_HUMAN 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.<ref>PMID:15632202</ref>  [[http://www.uniprot.org/uniprot/FRPD4_HUMAN FRPD4_HUMAN]] Positive regulator of dendritic spine morphogenesis and density. Required for the maintenance of excitatory synaptic transmission. Binds phosphatidylinositol 4,5-bisphosphate.<ref>PMID:19118189</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The adaptor protein LGN interacts via the N-terminal domain comprising eight tetratricopeptide-repeat (TPR) motifs with its partner proteins mInsc, NuMA, Frmpd1 and Frmpd4 in a mutually exclusive manner. Here, the crystal structure of the LGN TPR domain in complex with human Frmpd4 is described at 1.5 A resolution. In the complex, the LGN-binding region of Frmpd4 (amino-acid residues 990-1011) adopts an extended structure that runs antiparallel to LGN along the concave surface of the superhelix formed by the TPR motifs. Comparison with the previously determined structures of the LGN-Frmpd1, LGN-mInsc and LGN-NuMA complexes reveals that these partner proteins interact with LGN TPR1-6 via a common core binding region with consensus sequence (E/Q)XEX4-5(E/D/Q)X1-2(K/R)X0-1(V/I). In contrast to Frmpd1, Frmpd4 makes additional contacts with LGN via regions N- and C-terminal to the core sequence. The N-terminal extension is replaced by a specific alpha-helix in mInsc, which drastically increases the direct contacts with LGN TPR7/8, consistent with the higher affinity of mInsc for LGN. A crystal structure of Frmpd4-bound LGN in an oxidized form is also reported, although oxidation does not appear to strongly affect the interaction with Frmpd4.
-Authors: Takayanagi, H., Yuzawa, S., Sumimoto, H.
+Structural basis for the recognition of the scaffold protein Frmpd4/Preso1 by the TPR domain of the adaptor protein LGN.,Takayanagi H, Yuzawa S, Sumimoto H Acta Crystallogr F Struct Biol Commun. 2015 Feb;71(Pt 2):175-83. doi:, 10.1107/S2053230X14028143. Epub 2015 Jan 28. PMID:25664792<ref>PMID:25664792</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 4wnd" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human]]
+[[Category: Sumimoto, H]]
 [[Category: Takayanagi, H]]
 [[Category: Yuzawa, S]]
-[[Category: Sumimoto, H]]
+[[Category: Cell polarity]]
+[[Category: Cytoplasm and cell cortex]]
+[[Category: Signaling protein-protein binding complex]]
+[[Category: Tetratricopeptide repeat]]
+[[Category: Tpr]]

4wnd

From Proteopedia

Revision as of 16:58, 16 November 2017

Crystal structure of the TPR domain of LGN in complex with Frmpd4/Preso1 at 1.5 Angstrom resolution

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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