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[[Image:2nlu.jpg|left|200px]]<br /><applet load="2nlu" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2nlu" />
'''Domain-Swapped Dimer of the PWWP Module of Human Hepatoma-derived Growth Factor'''<br />


==Overview==
==Domain-Swapped Dimer of the PWWP Module of Human Hepatoma-derived Growth Factor==
Hepatoma-derived growth factor (hHDGF)-related proteins (HRPs) comprise a, new growth factor family sharing a highly conserved and ordered N-terminal, PWWP module (residues 1-100, previously referred to as a HATH domain) and, a variable disordered C-terminal domain. We have shown that the PWWP, module is responsible for heparin binding and have solved its structure in, solution. Here, we show that under physiological conditions, both the PWWP, module and hHDGF can form dimers. Surface plasmon resonance (SPR) studies, revealed that the PWWP dimer binds to heparin with affinity that is two, orders of magnitude higher (K(d)=13 nM) than that of the monomeric PWWP, module (K(d)=1.2 microM). The monomer-dimer equilibrium properties and NMR, structural data together suggest that the PWWP dimer is formed through a, domain-swapping mechanism. The domain-swapped PWWP dimer structures were, calculated on the basis of the NMR data. The results show that the two, PWWP protomers exchange their N-terminal hairpin to form a domain-swapped, dimer. The two monomers in a dimer are linked by the long flexible L2, loops, a feature supported by NMR relaxation data for the monomer and, dimer. The enhanced heparin-binding affinity of the dimer can be, rationalized in the framework of the dimer structure.
<StructureSection load='2nlu' size='340' side='right'caption='[[2nlu]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2nlu]] is a 2 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=2NLU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NLU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2nlu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nlu OCA], [https://pdbe.org/2nlu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nlu RCSB], [https://www.ebi.ac.uk/pdbsum/2nlu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nlu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HDGF_HUMAN HDGF_HUMAN] Heparin-binding protein, with mitogenic activity for fibroblasts. Acts as a transcriptional repressor.<ref>PMID:17974029</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/nl/2nlu_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=2nlu ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hepatoma-derived growth factor (hHDGF)-related proteins (HRPs) comprise a new growth factor family sharing a highly conserved and ordered N-terminal PWWP module (residues 1-100, previously referred to as a HATH domain) and a variable disordered C-terminal domain. We have shown that the PWWP module is responsible for heparin binding and have solved its structure in solution. Here, we show that under physiological conditions, both the PWWP module and hHDGF can form dimers. Surface plasmon resonance (SPR) studies revealed that the PWWP dimer binds to heparin with affinity that is two orders of magnitude higher (K(d)=13 nM) than that of the monomeric PWWP module (K(d)=1.2 microM). The monomer-dimer equilibrium properties and NMR structural data together suggest that the PWWP dimer is formed through a domain-swapping mechanism. The domain-swapped PWWP dimer structures were calculated on the basis of the NMR data. The results show that the two PWWP protomers exchange their N-terminal hairpin to form a domain-swapped dimer. The two monomers in a dimer are linked by the long flexible L2 loops, a feature supported by NMR relaxation data for the monomer and dimer. The enhanced heparin-binding affinity of the dimer can be rationalized in the framework of the dimer structure.


==About this Structure==
PWWP module of human hepatoma-derived growth factor forms a domain-swapped dimer with much higher affinity for heparin.,Sue SC, Lee WT, Tien SC, Lee SC, Yu JG, Wu WJ, Wu WG, Huang TH J Mol Biol. 2007 Mar 23;367(2):456-72. Epub 2007 Jan 9. PMID:17270212<ref>PMID:17270212</ref>
2NLU is a [http://en.wikipedia.org/wiki/Single_protein 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=2NLU OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
PWWP module of human hepatoma-derived growth factor forms a domain-swapped dimer with much higher affinity for heparin., Sue SC, Lee WT, Tien SC, Lee SC, Yu JG, Wu WJ, Wu WG, Huang TH, J Mol Biol. 2007 Mar 23;367(2):456-72. Epub 2007 Jan 9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17270212 17270212]
</div>
<div class="pdbe-citations 2nlu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Huang, T.H.]]
[[Category: Huang TH]]
[[Category: Lee, W.T.]]
[[Category: Lee WT]]
[[Category: Sue, S.C.]]
[[Category: Sue SC]]
[[Category: domain-swapping]]
[[Category: hath]]
[[Category: hdgf]]
[[Category: heparin]]
[[Category: hhdgf]]
[[Category: hormone/growth factor complex]]
[[Category: hrp]]
[[Category: pwwp]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:46:04 2008''

Latest revision as of 03:08, 28 December 2023

Domain-Swapped Dimer of the PWWP Module of Human Hepatoma-derived Growth FactorDomain-Swapped Dimer of the PWWP Module of Human Hepatoma-derived Growth Factor

Structural highlights

2nlu is a 2 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
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HDGF_HUMAN Heparin-binding protein, with mitogenic activity for fibroblasts. Acts as a transcriptional repressor.[1]

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

Hepatoma-derived growth factor (hHDGF)-related proteins (HRPs) comprise a new growth factor family sharing a highly conserved and ordered N-terminal PWWP module (residues 1-100, previously referred to as a HATH domain) and a variable disordered C-terminal domain. We have shown that the PWWP module is responsible for heparin binding and have solved its structure in solution. Here, we show that under physiological conditions, both the PWWP module and hHDGF can form dimers. Surface plasmon resonance (SPR) studies revealed that the PWWP dimer binds to heparin with affinity that is two orders of magnitude higher (K(d)=13 nM) than that of the monomeric PWWP module (K(d)=1.2 microM). The monomer-dimer equilibrium properties and NMR structural data together suggest that the PWWP dimer is formed through a domain-swapping mechanism. The domain-swapped PWWP dimer structures were calculated on the basis of the NMR data. The results show that the two PWWP protomers exchange their N-terminal hairpin to form a domain-swapped dimer. The two monomers in a dimer are linked by the long flexible L2 loops, a feature supported by NMR relaxation data for the monomer and dimer. The enhanced heparin-binding affinity of the dimer can be rationalized in the framework of the dimer structure.

PWWP module of human hepatoma-derived growth factor forms a domain-swapped dimer with much higher affinity for heparin.,Sue SC, Lee WT, Tien SC, Lee SC, Yu JG, Wu WJ, Wu WG, Huang TH J Mol Biol. 2007 Mar 23;367(2):456-72. Epub 2007 Jan 9. PMID:17270212[2]

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

References

  1. ↑ Yang J, Everett AD. Hepatoma-derived growth factor binds DNA through the N-terminal PWWP domain. BMC Mol Biol. 2007 Oct 31;8:101. PMID:17974029 doi:http://dx.doi.org/1471-2199-8-101
  2. ↑ Sue SC, Lee WT, Tien SC, Lee SC, Yu JG, Wu WJ, Wu WG, Huang TH. PWWP module of human hepatoma-derived growth factor forms a domain-swapped dimer with much higher affinity for heparin. J Mol Biol. 2007 Mar 23;367(2):456-72. Epub 2007 Jan 9. PMID:17270212 doi:10.1016/j.jmb.2007.01.010
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