2ci9: Difference between revisions

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New page: left|200px<br /> <applet load="2ci9" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ci9, resolution 1.50Å" /> '''NCK1 SH2-DOMAIN IN ...
 
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[[Image:2ci9.gif|left|200px]]<br />
<applet load="2ci9" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2ci9, resolution 1.50&Aring;" />
'''NCK1 SH2-DOMAIN IN COMPLEX WITH A DODECAPHOSPHOPEPTIDE FROM EPEC PROTEIN TIR'''<br />


==Overview==
==Nck1 SH2-domain in complex with a dodecaphosphopeptide from EPEC protein Tir==
Nck proteins are essential Src homology (SH) 2 and SH3 domain-bearing, adapters that modulate actin cytoskeleton dynamics by linking proline-rich, effector molecules to tyrosine kinases or phosphorylated signaling, intermediates. Two mammalian pathogens, enteropathogenic Escherichia coli, and vaccinia virus, exploit Nck as part of their infection strategy., Conflicting data indicate potential differences in the recognition, specificities of the SH2 domains of the isoproteins Nck1 (Nckalpha) and, Nck2 (Nckbeta and Grb4). We have characterized the binding specificities, of both SH2 domains and find them to be essentially indistinguishable., Crystal structures of both domains in complex with phosphopeptides derived, from the enteropathogenic E. coli protein Tir concur in identifying highly, conserved, specific recognition of the phosphopeptide. Differential, peptide recognition can therefore not account for the preference of either, Nck in particular signaling pathways. Binding studies using sequentially, mutated, high affinity phosphopeptides establish the sequence variability, tolerated in peptide recognition. Based on this binding motif, we identify, potential new binding partners of Nck1 and Nck2 and confirm this, experimentally for the Arf-GAP GIT1.
<StructureSection load='2ci9' size='340' side='right'caption='[[2ci9]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 
== Structural highlights ==
==Disease==
<table><tr><td colspan='2'>[[2ci9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CI9 FirstGlance]. <br>
Known disease associated with this structure: Pigmentation of skin, variation in OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609802 609802]]
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
==About this Structure==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ci9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ci9 OCA], [https://pdbe.org/2ci9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ci9 RCSB], [https://www.ebi.ac.uk/pdbsum/2ci9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ci9 ProSAT]</span></td></tr>
2CI9 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CI9 OCA].  
</table>
 
== Function ==
==Reference==
[https://www.uniprot.org/uniprot/NCK1_HUMAN NCK1_HUMAN] Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling.<ref>PMID:10026169</ref> <ref>PMID:16835242</ref> <ref>PMID:17803907</ref>
The phosphotyrosine peptide binding specificity of Nck1 and Nck2 Src homology 2 domains., Frese S, Schubert WD, Findeis AC, Marquardt T, Roske YS, Stradal TE, Heinz DW, J Biol Chem. 2006 Jun 30;281(26):18236-45. Epub 2006 Apr 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16636066 16636066]
== 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/ci/2ci9_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=2ci9 ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Findeis, A.C.]]
[[Category: Findeis AC]]
[[Category: Frese, S.]]
[[Category: Frese S]]
[[Category: Heinz, D.W.]]
[[Category: Heinz DW]]
[[Category: Marquardt, T.]]
[[Category: Marquardt T]]
[[Category: Roske, Y.S.]]
[[Category: Roske YS]]
[[Category: Schubert, W.D.]]
[[Category: Schubert W-D]]
[[Category: Stradal, T.E.B.]]
[[Category: Stradal TEB]]
[[Category: binding specificity]]
[[Category: host-pathogen]]
[[Category: phosphorylation]]
[[Category: repeat]]
[[Category: sh2-domain]]
[[Category: sh3 domain]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:15:41 2007''

Latest revision as of 06:38, 1 May 2024

Nck1 SH2-domain in complex with a dodecaphosphopeptide from EPEC protein Tir

2ci9, resolution 1.50Å

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