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2hmh

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Revision as of 00:31, 16 November 2017

Crystal structure of SOCS3 in complex with gp130(pTyr757) phosphopeptide.

Structural highlights

2hmh is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:	,
Gene:	Socs3 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SOCS3_MOUSE] SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL-6 signaling in vivo. 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 (By similarity). Seems to recognize IL6ST.^[1] ^[2] ^[3] ^[4] ^[5] [IL6RB_MOUSE] Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize gp130 for initiating signal transmission. Binds to IL6/IL6R (alpha chain) complex, resulting in the formation of high-affinity IL6 binding sites, and transduces the signal. Does not bind IL6. May have a role in embryonic development.

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

Suppressor of cytokine signaling (SOCS) proteins are indispensable negative regulators of cytokine-stimulated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathways. SOCS proteins (SOCS1-7 and CIS) consist of a variable N-terminal region, a central Src homology-2 (SH2) domain, and a C-terminal SOCS box. The N-terminal region in SOCS1 and SOCS3 includes the so-called kinase inhibitory region that has been shown to inhibit the catalytic activity of JAK2. Here, we present a crystal structure at 2.0 A resolution of the N-terminally extended SH2 domain of SOCS3 in complex with its phosphopeptide target on the cytokine receptor gp130. The structure reveals that major insertions in the EF and BG loops of the SOCS3 SH2 domain are responsible for binding to gp130 with high affinity and specificity. In addition, the structure provides insights into the possible mechanisms by which SOCS3 and SOCS1 inhibit JAK2 kinase activity.

Structural basis for phosphotyrosine recognition by suppressor of cytokine signaling-3.,Bergamin E, Wu J, Hubbard SR Structure. 2006 Aug;14(8):1285-92. PMID:16905102^[6]

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

References

↑ Nicholson SE, Willson TA, Farley A, Starr R, Zhang JG, Baca M, Alexander WS, Metcalf D, Hilton DJ, Nicola NA. Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL-6 signal transduction. EMBO J. 1999 Jan 15;18(2):375-85. PMID:9889194 doi:10.1093/emboj/18.2.375
↑ Emanuelli B, Peraldi P, Filloux C, Sawka-Verhelle D, Hilton D, Van Obberghen E. SOCS-3 is an insulin-induced negative regulator of insulin signaling. J Biol Chem. 2000 May 26;275(21):15985-91. PMID:10821852
↑ Marine JC, McKay C, Wang D, Topham DJ, Parganas E, Nakajima H, Pendeville H, Yasukawa H, Sasaki A, Yoshimura A, Ihle JN. SOCS3 is essential in the regulation of fetal liver erythropoiesis. Cell. 1999 Sep 3;98(5):617-27. PMID:10490101
↑ Croker BA, Krebs DL, Zhang JG, Wormald S, Willson TA, Stanley EG, Robb L, Greenhalgh CJ, Forster I, Clausen BE, Nicola NA, Metcalf D, Hilton DJ, Roberts AW, Alexander WS. SOCS3 negatively regulates IL-6 signaling in vivo. Nat Immunol. 2003 Jun;4(6):540-5. Epub 2003 May 18. PMID:12754505 doi:10.1038/ni931
↑ Seki Y, Inoue H, Nagata N, Hayashi K, Fukuyama S, Matsumoto K, Komine O, Hamano S, Himeno K, Inagaki-Ohara K, Cacalano N, O'Garra A, Oshida T, Saito H, Johnston JA, Yoshimura A, Kubo M. SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nat Med. 2003 Aug;9(8):1047-54. Epub 2003 Jun 29. PMID:12847520 doi:10.1038/nm896
↑ Bergamin E, Wu J, Hubbard SR. Structural basis for phosphotyrosine recognition by suppressor of cytokine signaling-3. Structure. 2006 Aug;14(8):1285-92. PMID:16905102 doi:10.1016/j.str.2006.06.011

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/2hmh"

@@ Line 1: / Line 1: @@
 ==Crystal structure of SOCS3 in complex with gp130(pTyr757) phosphopeptide.==
 <StructureSection load='2hmh' size='340' side='right' caption='[[2hmh]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Socs3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=2hmh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hmh OCA], [http://pdbe.org/2hmh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hmh RCSB], [http://www.ebi.ac.uk/pdbsum/2hmh PDBsum]</span></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=2hmh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hmh OCA], [http://pdbe.org/2hmh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hmh RCSB], [http://www.ebi.ac.uk/pdbsum/2hmh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2hmh ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 28: / Line 29: @@
 </div>
 <div class="pdbe-citations 2hmh" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Interleukin receptor|Interleukin receptor]]
 == References ==
 <references/>

2hmh

From Proteopedia

Revision as of 00:31, 16 November 2017

Crystal structure of SOCS3 in complex with gp130(pTyr757) phosphopeptide.

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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