1gp9

From Proteopedia

(Difference between revisions)

Current revision

A New Crystal Form of the Nk1 Splice Variant of Hgf/Sf Demonstrates Extensive Hinge Movement and Suggests that the Nk1 Dimer Originates by Domain Swapping

Structural highlights

1gp9 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

HGF_HUMAN Defects in HGF are the cause of deafness autosomal recessive type 39 (DFNB39) [MIM:608265. A form of profound prelingual 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.^[1]

Function

HGF_HUMAN Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization.^[2] ^[3]

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

NK1 is a splice variant of the polypeptide growth factor HGF/SF that consists of the N terminal (N) and first kringle (K) domains and retains receptor binding and signalling. While NK1 behaves as a monomer in solution, two independent crystallographic structures have previously shown an identical, tightly packed dimer. Here we report a novel orthorhombic crystal form of NK1 at 2.5 A resolution in which four NK1 protomers are packed in two distinct dimers in the asymmetric unit. Although the basic architecture of the new NK1 dimers is similar to the two described earlier, the new crystal form demonstrates extensive hinge movement between the N and K domain that leads to re-orientation of the receptor-binding sites. The hinge bending is evidence of the paucity of strong interactions between domains within the protomer, in contrast to the extensive interactions between protomers in the dimer. These observations are consistent with domain swapping in the dimer, such that the interdomain interactions of the monomer are replaced by equivalent interprotomer interactions in the dimer and offer a route for protein engineering of NK1 variants which may act as receptor antagonists.

A new crystal form of the NK1 splice variant of HGF/SF demonstrates extensive hinge movement and suggests that the NK1 dimer originates by domain swapping.,Watanabe K, Chirgadze DY, Lietha D, de Jonge H, Blundell TL, Gherardi E J Mol Biol. 2002 May 31;319(2):283-8. PMID:12051906^[4]

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

References

↑ Schultz JM, Khan SN, Ahmed ZM, Riazuddin S, Waryah AM, Chhatre D, Starost MF, Ploplis B, Buckley S, Velasquez D, Kabra M, Lee K, Hassan MJ, Ali G, Ansar M, Ghosh M, Wilcox ER, Ahmad W, Merlino G, Leal SM, Riazuddin S, Friedman TB, Morell RJ. Noncoding mutations of HGF are associated with nonsyndromic hearing loss, DFNB39. Am J Hum Genet. 2009 Jul;85(1):25-39. doi: 10.1016/j.ajhg.2009.06.003. Epub 2009 , Jul 2. PMID:19576567 doi:10.1016/j.ajhg.2009.06.003
↑ Stamos J, Lazarus RA, Yao X, Kirchhofer D, Wiesmann C. Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor. EMBO J. 2004 Jun 16;23(12):2325-35. Epub 2004 May 27. PMID:15167892 doi:10.1038/sj.emboj.7600243
↑ Tolbert WD, Daugherty-Holtrop J, Gherardi E, Vande Woude G, Xu HE. Structural basis for agonism and antagonism of hepatocyte growth factor. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13264-9. Epub 2010 Jul 12. PMID:20624990 doi:10.1073/pnas.1005183107
↑ Watanabe K, Chirgadze DY, Lietha D, de Jonge H, Blundell TL, Gherardi E. A new crystal form of the NK1 splice variant of HGF/SF demonstrates extensive hinge movement and suggests that the NK1 dimer originates by domain swapping. J Mol Biol. 2002 May 31;319(2):283-8. PMID:12051906 doi:http://dx.doi.org/10.1016/S0022-2836(02)00199-7

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/1gp9"

@@ Line 1: / Line 1: @@
-==A NEW CRYSTAL FORM OF THE NK1 SPLICE VARIANT OF HGF/SF DEMONSTRATES EXTENSIVE HINGE MOVEMENT AND SUGGESTS THAT THE NK1 DIMER ORIGINATES BY DOMAIN SWAPPING==
-<StructureSection load='1gp9' size='340' side='right' caption='[[1gp9]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+==A New Crystal Form of the Nk1 Splice Variant of Hgf/Sf Demonstrates Extensive Hinge Movement and Suggests that the Nk1 Dimer Originates by Domain Swapping==
+<StructureSection load='1gp9' size='340' side='right'caption='[[1gp9]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1gp9]] is a 4 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=1GP9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1GP9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1gp9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GP9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GP9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bht|1bht]], [[1gmn|1gmn]], [[1gmo|1gmo]], [[1nk1|1nk1]], [[2hgf|2hgf]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></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=1gp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gp9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1gp9 RCSB], [http://www.ebi.ac.uk/pdbsum/1gp9 PDBsum]</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=1gp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gp9 OCA], [https://pdbe.org/1gp9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gp9 RCSB], [https://www.ebi.ac.uk/pdbsum/1gp9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gp9 ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/HGF_HUMAN HGF_HUMAN] Defects in HGF are the cause of deafness autosomal recessive type 39 (DFNB39) [MIM:[https://omim.org/entry/608265 608265]. A form of profound prelingual 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:19576567</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/HGF_HUMAN HGF_HUMAN] Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization.<ref>PMID:15167892</ref> <ref>PMID:20624990</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gp/1gp9_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gp/1gp9_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1gp9 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 25: / Line 30: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1gp9" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 33: / Line 39: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Blundell, T L]]
+[[Category: Large Structures]]
-[[Category: Chirgadze, D Y]]
+[[Category: Blundell TL]]
-[[Category: Gherardi, E]]
+[[Category: Chirgadze DY]]
-[[Category: Lietha, D]]
+[[Category: Gherardi E]]
-[[Category: Watanabe, K]]
+[[Category: Lietha D]]
-[[Category: Domain swapping]]
+[[Category: Watanabe K]]
-[[Category: Glycoprotein]]
-[[Category: Growth factor]]
-[[Category: Hgf/sf]]
-[[Category: Hormone-growth factor complex]]
-[[Category: Hormone/growth factor]]
-[[Category: Kringle]]
-[[Category: Met]]
-[[Category: Nk1]]
-[[Category: Protein engineering]]

1gp9

From Proteopedia

Current revision

A New Crystal Form of the Nk1 Splice Variant of Hgf/Sf Demonstrates Extensive Hinge Movement and Suggests that the Nk1 Dimer Originates by Domain Swapping

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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