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| | ==Structure of the complex between NSP3 (SHEP1) and p130Cas== | | ==Structure of the complex between NSP3 (SHEP1) and p130Cas== |
| - | <StructureSection load='3t6g' size='340' side='right' caption='[[3t6g]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='3t6g' size='340' side='right'caption='[[3t6g]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3t6g]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T6G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T6G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3t6g]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T6G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3t6a|3t6a]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3t6a|3t6a]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SH2D3C, NSP3, UNQ272/PRO309/PRO34088 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BCAR1, CAS, CASS1, CRKAS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SH2D3C, NSP3, UNQ272/PRO309/PRO34088 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BCAR1, CAS, CASS1, CRKAS ([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=3t6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t6g OCA], [http://pdbe.org/3t6g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3t6g RCSB], [http://www.ebi.ac.uk/pdbsum/3t6g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3t6g 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=3t6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t6g OCA], [https://pdbe.org/3t6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t6g RCSB], [https://www.ebi.ac.uk/pdbsum/3t6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t6g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SH2D3_HUMAN SH2D3_HUMAN]] Eph receptor-binding protein which may be a positive regulator of TCR signaling. Binding to BCAR1 is required to induce membrane ruffling and promote EGF-dependent cell migration (By similarity). [[http://www.uniprot.org/uniprot/BCAR1_HUMAN BCAR1_HUMAN]] Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion. Implicated in induction of cell migration. Overexpression confers antiestrogen resistance on breast cancer cells.<ref>PMID:12832404</ref> <ref>PMID:17038317</ref> | + | [[https://www.uniprot.org/uniprot/SH2D3_HUMAN SH2D3_HUMAN]] Eph receptor-binding protein which may be a positive regulator of TCR signaling. Binding to BCAR1 is required to induce membrane ruffling and promote EGF-dependent cell migration (By similarity). [[https://www.uniprot.org/uniprot/BCAR1_HUMAN BCAR1_HUMAN]] Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion. Implicated in induction of cell migration. Overexpression confers antiestrogen resistance on breast cancer cells.<ref>PMID:12832404</ref> <ref>PMID:17038317</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Mace, P D]] | | [[Category: Mace, P D]] |
| | [[Category: Riedl, S J]] | | [[Category: Riedl, S J]] |
| Structural highlights
3t6g is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| Related: | |
| Gene: | SH2D3C, NSP3, UNQ272/PRO309/PRO34088 (HUMAN), BCAR1, CAS, CASS1, CRKAS (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SH2D3_HUMAN] Eph receptor-binding protein which may be a positive regulator of TCR signaling. Binding to BCAR1 is required to induce membrane ruffling and promote EGF-dependent cell migration (By similarity). [BCAR1_HUMAN] Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion. Implicated in induction of cell migration. Overexpression confers antiestrogen resistance on breast cancer cells.[1] [2]
Publication Abstract from PubMed
Members of the novel SH2-containing protein (NSP) and Crk-associated substrate (Cas) protein families form multidomain signaling platforms that mediate cell migration and invasion through a collection of distinct signaling motifs. Members of each family interact via their respective C-terminal domains, but the mechanism of this association has remained enigmatic. Here we present the crystal structures of the C-terminal domain from the NSP protein BCAR3 and the complex of NSP3 with p130Cas. BCAR3 adopts the Cdc25-homology fold of Ras GTPase exchange factors, but it has a 'closed' conformation incapable of enzymatic activity. The structure of the NSP3-p130Cas complex reveals that this closed conformation is instrumental for interaction of NSP proteins with a focal adhesion-targeting domain present in Cas proteins. This enzyme-to-adaptor conversion enables high-affinity, yet promiscuous, interactions between NSP and Cas proteins and represents an unprecedented mechanistic paradigm linking cellular signaling networks.
NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling.,Mace PD, Wallez Y, Dobaczewska MK, Lee JJ, Robinson H, Pasquale EB, Riedl SJ Nat Struct Mol Biol. 2011 Nov 13. doi: 10.1038/nsmb.2152. PMID:22081014[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Abassi YA, Rehn M, Ekman N, Alitalo K, Vuori K. p130Cas Couples the tyrosine kinase Bmx/Etk with regulation of the actin cytoskeleton and cell migration. J Biol Chem. 2003 Sep 12;278(37):35636-43. Epub 2003 Jun 28. PMID:12832404 doi:http://dx.doi.org/10.1074/jbc.M306438200
- ↑ Modzelewska K, Newman LP, Desai R, Keely PJ. Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas. J Biol Chem. 2006 Dec 8;281(49):37527-35. Epub 2006 Oct 12. PMID:17038317 doi:10.1074/jbc.M604342200
- ↑ Mace PD, Wallez Y, Dobaczewska MK, Lee JJ, Robinson H, Pasquale EB, Riedl SJ. NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling. Nat Struct Mol Biol. 2011 Nov 13. doi: 10.1038/nsmb.2152. PMID:22081014 doi:10.1038/nsmb.2152
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