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2jw4

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Revision as of 07:59, 7 April 2021

NMR solution structure of the N-terminal SH3 domain of human Nckalpha

Structural highlights

2jw4 is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	NCK1, NCK (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[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

The first SH3 domain (SH3.1) of Nckalpha specifically recognizes the proline-rich region of CD3varepsilon, a subunit of the T cell receptor complex. We have solved the NMR structure of Nckalpha SH3.1 that shows the characteristic SH3 fold consisting of two antiparallel beta-sheets tightly packed against each other. According to chemical shift mapping analysis, a peptide encompassing residues 150-166 of CD3varepsilon binds at the canonical SH3 binding site. An exhaustive comparison with the structures of other SH3 domains able and unable to bind CD3varepsilon reveals that Nckalpha SH3.1 recognises a non-canonical PxxPxxDY motif that orientates at the binding site as a class II ligand. A positively charged residue (K/R) at position -2 relative to the WW sequence at the beginning of strand beta3 is crucial for PxxDY recognition. A 14-mer optimised Nckalpha SH3.1 ligand was found using a multi-substitution approach. Based on NMR data, this improved ligand binds Nckalpha SH3.1 through a PxxPxRDY motif that combines specific stabilising interactions corresponding to both canonical class II, PxxPx(K/R), and non-canonical PxxPxxDY motifs. This explains its higher capacity for Nckalpha SH3.1 binding relative to the wild type sequence.

Interaction between the N-terminal SH3 domain of Nck-alpha and CD3-epsilon-derived peptides: non-canonical and canonical recognition motifs.,Santiveri CM, Borroto A, Simon L, Rico M, Alarcon B, Jimenez MA Biochim Biophys Acta. 2009 Jan;1794(1):110-7. Epub 2008 Oct 10. PMID:18955169^[4]

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
↑ Kremer BE, Adang LA, Macara IG. Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7. Cell. 2007 Sep 7;130(5):837-50. PMID:17803907 doi:http://dx.doi.org/10.1016/j.cell.2007.06.053
↑ Santiveri CM, Borroto A, Simon L, Rico M, Alarcon B, Jimenez MA. Interaction between the N-terminal SH3 domain of Nck-alpha and CD3-epsilon-derived peptides: non-canonical and canonical recognition motifs. Biochim Biophys Acta. 2009 Jan;1794(1):110-7. Epub 2008 Oct 10. PMID:18955169 doi:10.1016/j.bbapap.2008.09.016

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/2jw4"

@@ Line 1: / Line 1: @@
 ==NMR solution structure of the N-terminal SH3 domain of human Nckalpha==
-<StructureSection load='2jw4' size='340' side='right' caption='[[2jw4]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2jw4' size='340' side='right'caption='[[2jw4]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2jw4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JW4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JW4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2jw4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JW4 FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NCK1, NCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NCK1, NCK ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2jw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jw4 OCA], [http://pdbe.org/2jw4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jw4 RCSB], [http://www.ebi.ac.uk/pdbsum/2jw4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2jw4 ProSAT]</span></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=2jw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jw4 OCA], [https://pdbe.org/2jw4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jw4 RCSB], [https://www.ebi.ac.uk/pdbsum/2jw4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jw4 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 33: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Alarcon, B]]
 [[Category: Borroto, A]]

2jw4

From Proteopedia

Revision as of 07:59, 7 April 2021

NMR solution structure of the N-terminal SH3 domain of human Nckalpha

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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