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[[Image:1shy.gif|left|200px]]


{{Structure
==The Crystal Structure of HGF beta-chain in Complex with the Sema Domain of the Met Receptor.==
|PDB= 1shy |SIZE=350|CAPTION= <scene name='initialview01'>1shy</scene>, resolution 3.22&Aring;
<StructureSection load='1shy' size='340' side='right'caption='[[1shy]], [[Resolution|resolution]] 3.22&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND=  
<table><tr><td colspan='2'>[[1shy]] is a 2 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=1SHY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SHY FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.22&#8491;</td></tr>
|GENE= HGF, HPTA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), MET ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1shy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1shy OCA], [https://pdbe.org/1shy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1shy RCSB], [https://www.ebi.ac.uk/pdbsum/1shy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1shy ProSAT]</span></td></tr>
|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd00190 Tryp_SPc], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam01437 PSI], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam01403 Sema]</span>
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1shy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1shy OCA], [http://www.ebi.ac.uk/pdbsum/1shy PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=1shy RCSB]</span>
== 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/sh/1shy_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/main_output.php?pdb_ID=1shy ConSurf].
<div style="clear:both"></div>


'''The Crystal Structure of HGF beta-chain in Complex with the Sema Domain of the Met Receptor.'''
==See Also==
 
*[[Hepatocyte growth factor|Hepatocyte growth factor]]
 
*[[Hepatocyte growth factor receptor 3D structures|Hepatocyte growth factor receptor 3D structures]]
==Overview==
== References ==
The Met tyrosine kinase receptor and its ligand, hepatocyte growth factor (HGF), play important roles in normal development and in tumor growth and metastasis. HGF-dependent signaling requires proteolysis from an inactive single-chain precursor into an active alpha/beta-heterodimer. We show that the serine protease-like HGF beta-chain alone binds Met, and report its crystal structure in complex with the Sema and PSI domain of the Met receptor. The Met Sema domain folds into a seven-bladed beta-propeller, where the bottom face of blades 2 and 3 binds to the HGF beta-chain 'active site region'. Mutation of HGF residues in the area that constitutes the active site region in related serine proteases significantly impairs HGF beta binding to Met. Key binding loops in this interface undergo conformational rearrangements upon maturation and explain the necessity of proteolytic cleavage for proper HGF signaling. A crystallographic dimer interface between two HGF beta-chains brings two HGF beta:Met complexes together, suggesting a possible mechanism of Met receptor dimerization and activation by HGF.
<references/>
 
__TOC__
==Disease==
</StructureSection>
Known diseases associated with this structure: Autism, suseptibility to, 9 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164860 164860]], Fibromatosis, gingival OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=182530 182530]], Hepatocellular carcinoma, childhood type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164860 164860]], Noonan syndrome 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=182530 182530]], Renal cell carcinoma, papillary, familial and sporadic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164860 164860]]
 
==About this Structure==
1SHY is a [[Protein complex]] structure of sequences 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=1SHY OCA].
 
==Reference==
Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor., Stamos J, Lazarus RA, Yao X, Kirchhofer D, Wiesmann C, EMBO J. 2004 Jun 16;23(12):2325-35. Epub 2004 May 27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15167892 15167892]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Stamos, J.]]
[[Category: Stamos J]]
[[Category: Wiesmann, C.]]
[[Category: Wiesmann C]]
[[Category: protease]]
[[Category: psi domain]]
[[Category: receptor ectodomain growth factor]]
[[Category: sema domain]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 26 06:05:08 2008''

Latest revision as of 09:14, 3 April 2024

The Crystal Structure of HGF beta-chain in Complex with the Sema Domain of the Met Receptor.The Crystal Structure of HGF beta-chain in Complex with the Sema Domain of the Met Receptor.

Structural highlights

1shy is a 2 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 3.22Å
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.

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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

1shy, resolution 3.22Å

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