7m6t
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Crystal structure of SOCS2/ElonginB/ElonginC bound to a non-canonical peptide that enhances phospho-peptide binding== |
| - | <StructureSection load='7m6t' size='340' side='right'caption='[[7m6t]]' scene=''> | + | <StructureSection load='7m6t' size='340' side='right'caption='[[7m6t]], [[Resolution|resolution]] 3.19Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7m6t]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7M6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M6T FirstGlance]. <br> |
| - | </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=7m6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m6t OCA], [https://pdbe.org/7m6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m6t RCSB], [https://www.ebi.ac.uk/pdbsum/7m6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m6t ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.194Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7m6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m6t OCA], [https://pdbe.org/7m6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m6t RCSB], [https://www.ebi.ac.uk/pdbsum/7m6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m6t ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SOCS2_HUMAN SOCS2_HUMAN] SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Suppressor of cytokine signaling (SOCS)2 protein is a key negative regulator of the growth hormone (GH) and Janus kinase (JAK)-Signal Transducers and Activators of Transcription (STAT) signaling cascade. The central SOCS2-Src homology 2 (SH2) domain is characteristic of the SOCS family proteins and is an important module that facilitates recognition of targets bearing phosphorylated tyrosine (pTyr) residues. Here we identify an exosite on the SOCS2-SH2 domain which, when bound to a non-phosphorylated peptide (F3), enhances SH2 affinity for canonical phosphorylated ligands. Solution of the SOCS2/F3 crystal structure reveals F3 as an alpha-helix which binds on the opposite side of the SH2 domain to the phosphopeptide binding site. F3:exosite binding appears to stabilise the SOCS2-SH2 domain, resulting in slower dissociation of phosphorylated ligands and consequently, enhances binding affinity. This biophysical enhancement of SH2:pTyr binding affinity translates to increase SOCS2 inhibition of GH signaling. | ||
| + | |||
| + | Discovery of an exosite on the SOCS2-SH2 domain that enhances SH2 binding to phosphorylated ligands.,Linossi EM, Li K, Veggiani G, Tan C, Dehkhoda F, Hockings C, Calleja DJ, Keating N, Feltham R, Brooks AJ, Li SS, Sidhu SS, Babon JJ, Kershaw NJ, Nicholson SE Nat Commun. 2021 Dec 2;12(1):7032. doi: 10.1038/s41467-021-26983-5. PMID:34857742<ref>PMID:34857742</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7m6t" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Elongation factor 3D structures|Elongation factor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Synthetic construct]] |
| + | [[Category: Kershaw NJ]] | ||
| + | [[Category: Li K]] | ||
| + | [[Category: Linossi EM]] | ||
| + | [[Category: Nicholson SE]] | ||
Current revision
Crystal structure of SOCS2/ElonginB/ElonginC bound to a non-canonical peptide that enhances phospho-peptide binding
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