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[[Image:2hgf.jpg|left|200px]]
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{{STRUCTURE_2hgf|  PDB=2hgf  |  SCENE=  }}
'''HAIRPIN LOOP CONTAINING DOMAIN OF HEPATOCYTE GROWTH FACTOR, NMR, MINIMIZED AVERAGE STRUCTURE'''


==HAIRPIN LOOP CONTAINING DOMAIN OF HEPATOCYTE GROWTH FACTOR, NMR, MINIMIZED AVERAGE STRUCTURE==
<StructureSection load='2hgf' size='340' side='right'caption='[[2hgf]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2hgf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HGF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 1 model</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=2hgf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hgf OCA], [https://pdbe.org/2hgf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hgf RCSB], [https://www.ebi.ac.uk/pdbsum/2hgf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hgf 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/hg/2hgf_consurf.spt"</scriptWhenChecked>
    <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/main_output.php?pdb_ID=2hgf ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: Hepatocyte growth factor (HGF) is a multipotent growth factor that transduces a wide range of biological signals, including mitogenesis, motogenesis, and morphogenesis. The N-terminal (N) domain of HGF, containing a hairpin-loop region, is important for receptor binding and the potent biological activities of HGF. The N domain is also the primary binding site for heparin or heparan sulfate, which enhances, receptor/ligand oligomerization and modulates receptor-dependent mitogenesis. The rational design of artificial modulators of HGF signaling requires a detailed understanding of the structures of HGF and its receptor, as well as the role of heparin proteoglycan; this study represents the first step towards that goal. RESULTS: We report here a high-resolution structure of the N domain of HGF. This first structure of HGF reveals a novel folding topology with a distinct pattern of charge distribution and indicates a possible heparin-binding site. CONCLUSIONS: The hairpin-loop region of the N domain plays a major role in stabilizing the structure and contributes to a putative heparin-binding site, which explains why it is required for biological functions. These results suggest several basic and/or polar residues that may be important for use in further mutational studies of heparin binding.


==Overview==
The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site.,Zhou H, Mazzulla MJ, Kaufman JD, Stahl SJ, Wingfield PT, Rubin JS, Bottaro DP, Byrd RA Structure. 1998 Jan 15;6(1):109-16. PMID:9493272<ref>PMID:9493272</ref>
BACKGROUND: Hepatocyte growth factor (HGF) is a multipotent growth factor that transduces a wide range of biological signals, including mitogenesis, motogenesis, and morphogenesis. The N-terminal (N) domain of HGF, containing a hairpin-loop region, is important for receptor binding and the potent biological activities of HGF. The N domain is also the primary binding site for heparin or heparan sulfate, which enhances, receptor/ligand oligomerization and modulates receptor-dependent mitogenesis. The rational design of artificial modulators of HGF signaling requires a detailed understanding of the structures of HGF and its receptor, as well as the role of heparin proteoglycan; this study represents the first step towards that goal. RESULTS: We report here a high-resolution structure of the N domain of HGF. This first structure of HGF reveals a novel folding topology with a distinct pattern of charge distribution and indicates a possible heparin-binding site. CONCLUSIONS: The hairpin-loop region of the N domain plays a major role in stabilizing the structure and contributes to a putative heparin-binding site, which explains why it is required for biological functions. These results suggest several basic and/or polar residues that may be important for use in further mutational studies of heparin binding.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2HGF is a [[Single protein]] structure of 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=2HGF OCA].
</div>
<div class="pdbe-citations 2hgf" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site., Zhou H, Mazzulla MJ, Kaufman JD, Stahl SJ, Wingfield PT, Rubin JS, Bottaro DP, Byrd RA, Structure. 1998 Jan 15;6(1):109-16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9493272 9493272]
*[[Hepatocyte growth factor|Hepatocyte growth factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Bottaro, D P.]]
[[Category: Bottaro DP]]
[[Category: Byrd, R A.]]
[[Category: Byrd RA]]
[[Category: Kaufman, J D.]]
[[Category: Kaufman JD]]
[[Category: Mazzulla, M J.]]
[[Category: Mazzulla MJ]]
[[Category: Rubin, J S.]]
[[Category: Rubin JS]]
[[Category: Stahl, S J.]]
[[Category: Stahl SJ]]
[[Category: Wingfield, P T.]]
[[Category: Wingfield PT]]
[[Category: Zhou, H.]]
[[Category: Zhou H]]
[[Category: Hairpin loop]]
[[Category: Heparin binding]]
[[Category: Hepatocyte growth factor]]
[[Category: Nk1]]
[[Category: Plasminogen related]]
[[Category: Scatter factor]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 06:15:41 2008''

Latest revision as of 10:55, 23 October 2024

HAIRPIN LOOP CONTAINING DOMAIN OF HEPATOCYTE GROWTH FACTOR, NMR, MINIMIZED AVERAGE STRUCTUREHAIRPIN LOOP CONTAINING DOMAIN OF HEPATOCYTE GROWTH FACTOR, NMR, MINIMIZED AVERAGE STRUCTURE

Structural highlights

2hgf is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR, 1 model
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

BACKGROUND: Hepatocyte growth factor (HGF) is a multipotent growth factor that transduces a wide range of biological signals, including mitogenesis, motogenesis, and morphogenesis. The N-terminal (N) domain of HGF, containing a hairpin-loop region, is important for receptor binding and the potent biological activities of HGF. The N domain is also the primary binding site for heparin or heparan sulfate, which enhances, receptor/ligand oligomerization and modulates receptor-dependent mitogenesis. The rational design of artificial modulators of HGF signaling requires a detailed understanding of the structures of HGF and its receptor, as well as the role of heparin proteoglycan; this study represents the first step towards that goal. RESULTS: We report here a high-resolution structure of the N domain of HGF. This first structure of HGF reveals a novel folding topology with a distinct pattern of charge distribution and indicates a possible heparin-binding site. CONCLUSIONS: The hairpin-loop region of the N domain plays a major role in stabilizing the structure and contributes to a putative heparin-binding site, which explains why it is required for biological functions. These results suggest several basic and/or polar residues that may be important for use in further mutational studies of heparin binding.

The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site.,Zhou H, Mazzulla MJ, Kaufman JD, Stahl SJ, Wingfield PT, Rubin JS, Bottaro DP, Byrd RA Structure. 1998 Jan 15;6(1):109-16. PMID:9493272[4]

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

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
  4. ↑ Zhou H, Mazzulla MJ, Kaufman JD, Stahl SJ, Wingfield PT, Rubin JS, Bottaro DP, Byrd RA. The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site. Structure. 1998 Jan 15;6(1):109-16. PMID:9493272
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