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1z3k

From Proteopedia

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Structural Insight into the Binding Diversity between the Tyr-Phosphorylated Human EphrinBs and Nck2 SH2 Domain

Structural highlights

1z3k 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
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NCK2_HUMAN Adapter protein which associates with tyrosine-phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling.^[1] ^[2]

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

The binding interaction between the Nck2 SH2 domain and the phosphorylated ephrinB initiates a critical pathway for the reverse signaling network mediated by Eph receptor-ephrinB. Previously, the NMR structure and Tyr phosphorylations of the human ephrinB cytoplasmic domain have been studied. To obtain a complete story, it would be of significant interest to determine the structure of the Nck2 SH2 domain that shows a low sequence identity to other SH2 domains with known structures. Here, we report the determination of the solution structure of the human Nck2 SH2 domain and investigate its interactions with three phosphorylated ephrinB fragments by NMR spectroscopy. The results indicate that: 1) although the human Nck2 SH2 domain adopts a core tertiary fold common to all SH2 domains, it owns some unique properties such as a shorter C-terminal helix and unusual electrostatic potential surface. However, the most striking finding is that the C-terminal tail of the human Nck2 SH2 domain adopts a short antiparallel beta-sheet that, to the best of our knowledge, has never been identified in other SH2 domains. The truncation study suggests that one function of the C-terminal tail is to control the folding/solubility of the SH2 domain. 2) In addition to [Tyr(P)304]ephrinB2(301-322) and [Tyr(P)316]ephrinB2(301-322), here we identified [Tyr(P)330]ephrinB2(324-333) also capable of binding to the SH2 domain. The detailed NMR study indicated that the binding mechanisms for the three ephrinB fragments might be different. The binding with [Tyr(P)304]-ephrinB2(301-322) and [Tyr(P)316]ephrinB2(301-322) might be mostly involved in the residues over the N-half of the SH2 domain and provoked a significant increase in the backbone and side chain dynamics of the SH2 domain on the microsecond-millisecond time scale. In contrast, binding with [Tyr(P)330]ephrinB2(324-333) might have most residues over both halves engaged but induced less profound conformational dynamics on the mus-ms time scale.

Structural insight into the binding diversity between the Tyr-phosphorylated human ephrinBs and Nck2 SH2 domain.,Ran X, Song J J Biol Chem. 2005 May 13;280(19):19205-12. Epub 2005 Mar 11. PMID:15764601^[3]

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

References

↑ Braverman LE, Quilliam LA. Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck. J Biol Chem. 1999 Feb 26;274(9):5542-9. PMID:10026169
↑ Latreille M, Larose L. Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling and cell survival to endoplasmic reticulum stress. J Biol Chem. 2006 Sep 8;281(36):26633-44. Epub 2006 Jul 11. PMID:16835242 doi:http://dx.doi.org/M513556200
↑ Ran X, Song J. Structural insight into the binding diversity between the Tyr-phosphorylated human ephrinBs and Nck2 SH2 domain. J Biol Chem. 2005 May 13;280(19):19205-12. Epub 2005 Mar 11. PMID:15764601 doi:10.1074/jbc.M500330200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1z3k"

Categories: Homo sapiens | Large Structures | Ran X | Song J

@@ Line 1: / Line 1: @@
 ==Structural Insight into the Binding Diversity between the Tyr-Phosphorylated Human EphrinBs and Nck2 SH2 Domain==
-<StructureSection load='1z3k' size='340' side='right' caption='[[1z3k]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='1z3k' size='340' side='right'caption='[[1z3k]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1z3k]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z3K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z3K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1z3k]] 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=1Z3K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z3K FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1z3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z3k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1z3k RCSB], [http://www.ebi.ac.uk/pdbsum/1z3k PDBsum]</span></td></tr>
+</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=1z3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z3k OCA], [https://pdbe.org/1z3k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z3k RCSB], [https://www.ebi.ac.uk/pdbsum/1z3k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z3k ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/NCK2_HUMAN NCK2_HUMAN]] Adapter protein which associates with tyrosine-phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling.<ref>PMID:10026169</ref> <ref>PMID:16835242</ref>
+[https://www.uniprot.org/uniprot/NCK2_HUMAN NCK2_HUMAN] Adapter protein which associates with tyrosine-phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling.<ref>PMID:10026169</ref> <ref>PMID:16835242</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/z3/1z3k_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z3/1z3k_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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=1z3k ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 25: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1z3k" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 30: / Line 33: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Ran, X]]
+[[Category: Large Structures]]
-[[Category: Song, J]]
+[[Category: Ran X]]
-[[Category: Eph receptor-ephrin mediated signaling]]
+[[Category: Song J]]
-[[Category: Nck2]]
-[[Category: Sh2 domain]]
-[[Category: Structural genomic]]
-[[Category: Unknown function]]

1z3k

From Proteopedia

Current revision

Structural Insight into the Binding Diversity between the Tyr-Phosphorylated Human EphrinBs and Nck2 SH2 Domain

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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