2h46: Difference between revisions

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New page: left|200px<br /> <applet load="2h46" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h46, resolution 1.900Å" /> '''Native domain-swap...
 
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[[Image:2h46.gif|left|200px]]<br />
<applet load="2h46" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2h46, resolution 1.900&Aring;" />
'''Native domain-swapped dimer crystal structure of the Grb2 SH2 domain'''<br />


==Overview==
==Native domain-swapped dimer crystal structure of the Grb2 SH2 domain==
The SH2 domain of growth factor receptor-bound protein 2 (Grb2) has been, the focus of numerous studies, primarily because of the important roles it, plays in signal transduction. More recently, it has emerged as a useful, protein to study the consequences of ligand preorganization upon, energetics and structure in protein-ligand interactions. The Grb2-SH2, domain is known to form a domain-swapped dimer, and as part of our, investigations toward correlating structure and energetics in biological, systems, we examined the effects that domain-swapping dimerization of the, Grb2-SH2 domain had upon ligand binding affinities. Isothermal titration, calorimetry was performed using Grb2-SH2 in both its monomeric and, domain-swapped dimeric forms and a phosphorylated tripeptide, AcNH-pTyr-Val-Asn-NH(2) that is similar to the Shc sequence recognized by, Grb2-SH2 in vivo. The two binding sites of domain-swapped dimer exhibited, a 4- and a 13-fold reduction in ligand affinity compared to monomer., Crystal structures of peptide-bound and uncomplexed forms of Grb2-SH2, domain-swapped dimer were obtained and reveal that the orientation of, residues V122, V123, and R142 may influence the conformation of W121, an, amino acid that is believed to play an important role in Grb2-SH2 ligand, sequence specificity. These findings suggest that domain-swapping of, Grb2-SH2 not only results in a lower affinity for a Shc-derived ligand, but it may also affect ligand specificity.
<StructureSection load='2h46' size='340' side='right'caption='[[2h46]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2h46]] is a 1 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=2H46 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H46 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=2h46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h46 OCA], [https://pdbe.org/2h46 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h46 RCSB], [https://www.ebi.ac.uk/pdbsum/2h46 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h46 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GRB2_HUMAN GRB2_HUMAN] Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.<ref>PMID:1322798</ref> <ref>PMID:8178156</ref> <ref>PMID:19815557</ref>  Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death.<ref>PMID:1322798</ref> <ref>PMID:8178156</ref> <ref>PMID:19815557</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/h4/2h46_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=2h46 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2H46 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with GOL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2H46 OCA].
*[[Growth factor receptor-bound proteins 3D structures|Growth factor receptor-bound proteins 3D structures]]
 
== References ==
==Reference==
<references/>
Structural and energetic aspects of Grb2-SH2 domain-swapping., Benfield AP, Whiddon BB, Clements JH, Martin SF, Arch Biochem Biophys. 2007 Jun 1;462(1):47-53. Epub 2007 Apr 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17466257 17466257]
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Benfield, A.P.]]
[[Category: Benfield AP]]
[[Category: Martin, S.F.]]
[[Category: Martin SF]]
[[Category: Whiddon, B.B.]]
[[Category: Whiddon BB]]
[[Category: GOL]]
[[Category: helix-sheet-helix]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:26:06 2007''

Latest revision as of 09:30, 14 February 2024

Native domain-swapped dimer crystal structure of the Grb2 SH2 domain

2h46, resolution 1.90Å

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