1i85: Difference between revisions

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-[[Image:1i85.jpg|left|200px]]<br /><applet load="1i85" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="1i85, resolution 3.2&Aring;" />
-'''CRYSTAL STRUCTURE OF THE CTLA-4/B7-2 COMPLEX'''<br />
-==Overview==
+==CRYSTAL STRUCTURE OF THE CTLA-4/B7-2 COMPLEX==
-Regulation of T-cell activity is dependent on antigen-independent co-stimulatory signals provided by the disulphide-linked homodimeric T-cell surface receptors, CD28 and CTLA-4 (ref. 1). Engagement of CD28 with B7-1 and B7-2 ligands on antigen-presenting cells (APCs) provides a stimulatory signal for T-cell activation, whereas subsequent engagement of CTLA-4 with these same ligands results in attenuation of the response. Given their central function in immune modulation, CTLA-4- and CD28-associated signalling pathways are primary therapeutic targets for preventing autoimmune disease, graft versus host disease, graft rejection and promoting tumour immunity. However, little is known about the cell-surface organization of these receptor/ligand complexes and the structural basis for signal transduction. Here we report the 3.2-A resolution structure of the complex between the disulphide-linked homodimer of human CTLA-4 and the receptor-binding domain of human B7-2. The unusual dimerization properties of both CTLA-4 and B7-2 place their respective ligand-binding sites distal to the dimer interface in each molecule and promote the formation of an alternating arrangement of bivalent CTLA-4 and B7-2 dimers that extends throughout the crystal. Direct observation of this CTLA-4/B7-2 network provides a model for the periodic organization of these molecules within the immunological synapse and suggests a distinct mechanism for signalling by dimeric cell-surface receptors.
+<StructureSection load='1i85' size='340' side='right'caption='[[1i85]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1i85]] is a 4 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=1I85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I85 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]] 3.2&#8491;</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=1i85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i85 OCA], [https://pdbe.org/1i85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i85 RCSB], [https://www.ebi.ac.uk/pdbsum/1i85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i85 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CD86_HUMAN CD86_HUMAN] Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4. May play a critical role in the early events of T-cell activation and costimulation of naive T-cells, such as deciding between immunity and anergy that is made by T-cells within 24 hours after activation. Isoform 2 interferes with the formation of CD86 clusters, and thus acts as a negative regulator of T-cell activation.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i8/1i85_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1i85 ConSurf].
+<div style="clear:both"></div>
-==Disease==
+==See Also==
-Known diseases associated with this structure: Celiac disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=123890 123890]], Diabetes mellitus, insulin-dependent, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=123890 123890]], Graves disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=123890 123890]], Hypothyroidism, autoimmune OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=123890 123890]]
+*[[CTLA-4|CTLA-4]]
+__TOC__
-==About this Structure==
+</StructureSection>
-I85 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I85 OCA].
-==Reference==
-Structural basis for co-stimulation by the human CTLA-4/B7-2 complex., Schwartz JC, Zhang X, Fedorov AA, Nathenson SG, Almo SC, Nature. 2001 Mar 29;410(6828):604-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11279501 11279501]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Almo, S C.]]
+[[Category: Almo SC]]
-[[Category: Fedorov, A A.]]
+[[Category: Fedorov AA]]
-[[Category: Nathenson, S G.]]
+[[Category: Nathenson SG]]
-[[Category: Schwartz, J C.D.]]
+[[Category: Schwartz J-CD]]
-[[Category: Zhang, X.]]
+[[Category: Zhang X]]
-[[Category: ig v-type domain]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:09:00 2008''