6i5n
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6i5n is ON HOLD Authors: Kung, W.W., Ramachandran, S., Makukhin, N., Ciulli, A., Bruno, E. Description: Crystal structure of SOCS2:Elongin C:Elongi...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of SOCS2:Elongin C:Elongin B in complex with growth hormone receptor peptide== | |
| + | <StructureSection load='6i5n' size='340' side='right'caption='[[6i5n]], [[Resolution|resolution]] 1.98Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6i5n]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I5N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I5N FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.98Å</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=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VLM:VALINYLAMINE'>VLM</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=6i5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i5n OCA], [https://pdbe.org/6i5n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i5n RCSB], [https://www.ebi.ac.uk/pdbsum/6i5n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i5n ProSAT]</span></td></tr> | ||
| + | </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 == | ||
| + | The suppressor of cytokine signaling 2 (SOCS2) acts as substrate recognition subunit of a Cullin5 E3 ubiquitin ligase complex. SOCS2 binds to phosphotyrosine-modified epitopes as degrons for ubiquitination and proteasomal degradation, yet the molecular basis of substrate recognition has remained elusive. Here, we report co-crystal structures of SOCS2-ElonginB-ElonginC in complex with phosphorylated peptides from substrates growth hormone receptor (GHR-pY595) and erythropoietin receptor (EpoR-pY426) at 1.98 A and 2.69 A, respectively. Both peptides bind in an extended conformation recapitulating the canonical SH2 domain-pY pose, but capture different conformations of the EF loop via specific hydrophobic interactions. The flexible BG loop is fully defined in the electron density, and does not contact the substrate degron directly. Cancer-associated SNPs located around the pY pocket weaken substrate-binding affinity in biophysical assays. Our findings reveal insights into substrate recognition and specificity by SOCS2, and provide a blueprint for small molecule ligand design. | ||
| - | + | Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase.,Kung WW, Ramachandran S, Makukhin N, Bruno E, Ciulli A Nat Commun. 2019 Jun 10;10(1):2534. doi: 10.1038/s41467-019-10190-4. PMID:31182716<ref>PMID:31182716</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6i5n" style="background-color:#fffaf0;"></div> |
| - | [[Category: Bruno | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: Kung | + | *[[Elongation factor 3D structures|Elongation factor 3D structures]] |
| - | [[Category: Makukhin | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bruno E]] | ||
| + | [[Category: Ciulli A]] | ||
| + | [[Category: Kung WW]] | ||
| + | [[Category: Makukhin N]] | ||
| + | [[Category: Ramachandran S]] | ||
Current revision
Crystal structure of SOCS2:Elongin C:Elongin B in complex with growth hormone receptor peptide
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