2x44: Difference between revisions

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-[[Image:2x44.png|left|200px]]
-<!--
+==Structure of a strand-swapped dimeric form of CTLA-4==
-The line below this paragraph, containing "STRUCTURE_2x44", creates the "Structure Box" on the page.
+<StructureSection load='2x44' size='340' side='right'caption='[[2x44]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2x44]] is a 1 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=2X44 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X44 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#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=2x44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x44 OCA], [https://pdbe.org/2x44 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x44 RCSB], [https://www.ebi.ac.uk/pdbsum/2x44 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x44 ProSAT]</span></td></tr>
-{{STRUCTURE_2x44|  PDB=2x44  |  SCENE=  }}
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/CTLA4_HUMAN CTLA4_HUMAN] Genetic variation in CTLA4 influences susceptibility to systemic lupus erythematosus (SLE) [MIM:[https://omim.org/entry/152700 152700]. SLE is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. SLE is thought to represent a failure of the regulatory mechanisms of the autoimmune system.<ref>PMID:10924276</ref>   Note=Genetic variations in CTLA4 may influence susceptibility to Graves disease, an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism.<ref>PMID:10924276</ref>   Genetic variation in CTLA4 is the cause of susceptibility to diabetes mellitus insulin-dependent type 12 (IDDM12) [MIM:[https://omim.org/entry/601388 601388]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:10924276</ref> <ref>PMID:9259273</ref>   Genetic variation in CTLA4 is the cause of susceptibility to celiac disease type 3 (CELIAC3) [MIM:[https://omim.org/entry/609755 609755]. It is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins. In its classic form, celiac disease is characterized in children by malabsorption and failure to thrive.
+== Function ==
+[https://www.uniprot.org/uniprot/CTLA4_HUMAN CTLA4_HUMAN] Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28.<ref>PMID:1714933</ref> <ref>PMID:16551244</ref>
+== 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/x4/2x44_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2x44 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+We present the crystal structure of an immunoglobulin light-chain-like domain, CTLA-4, as a strand-swapped dimer displaying cis-trans proline isomerisation and native-like hydrogen bonding. We also show that CTLA-4 can form amyloid-like fibres and amorphous deposits explainable by the same strand swapping. Our results suggest a molecular basis for the pathological aggregation of immunoglobulin domains and why amyloid-like fibres are more often composed of homologous rather than heterologous subunits.
-===STRUCTURE OF A STRAND-SWAPPED DIMERIC FORM OF CTLA-4===
+Domain metastability: a molecular basis for immunoglobulin deposition?,Sonnen AF, Yu C, Evans EJ, Stuart DI, Davis SJ, Gilbert RJ J Mol Biol. 2010 Jun 4;399(2):207-13. Epub 2010 Apr 13. PMID:20394753<ref>PMID:20394753</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2x44" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20394753}}, adds the Publication Abstract to the page
+*[[CTLA-4|CTLA-4]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20394753 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20394753}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[2x44]] is a 1 chain structure with sequence 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=2X44 OCA].
-==Reference==
-<ref group="xtra">PMID:020394753</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Davis, S J.]]
+[[Category: Large Structures]]
-[[Category: Evans, E J.]]
+[[Category: Davis SJ]]
-[[Category: Gilbert, R J.C.]]
+[[Category: Evans EJ]]
-[[Category: Sonnen, A F.P.]]
+[[Category: Gilbert RJC]]
-[[Category: Stuart, D I.]]
+[[Category: Sonnen AF-P]]
-[[Category: Yu, C.]]
+[[Category: Stuart DI]]
-[[Category: Amyloidogenic]]
+[[Category: Yu C]]
-[[Category: Glycoprotein]]
-[[Category: Immune system]]
-[[Category: Immunoglobulin domain]]
-[[Category: Membrane]]
-[[Category: Systemic lupus erythematosus]]
-[[Category: Transmembrane]]