1ar2: Difference between revisions

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-{{Seed}}
-[[Image:1ar2.png|left|200px]]
-<!--
+==DISULFIDE-FREE IMMUNOGLOBULIN FRAGMENT==
-The line below this paragraph, containing "STRUCTURE_1ar2", creates the "Structure Box" on the page.
+<StructureSection load='1ar2' size='340' side='right'caption='[[1ar2]], [[Resolution|resolution]] 2.80&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'>[[1ar2]] 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=1AR2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AR2 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]] 2.8&#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=1ar2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ar2 OCA], [https://pdbe.org/1ar2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ar2 RCSB], [https://www.ebi.ac.uk/pdbsum/1ar2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ar2 ProSAT]</span></td></tr>
-{{STRUCTURE_1ar2|  PDB=1ar2  |  SCENE=  }}
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/KVD33_HUMAN KVD33_HUMAN] V region of the variable domain of immunoglobulin light chains that participates in the antigen recognition (PubMed:24600447). Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:20176268, PubMed:22158414). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:20176268, PubMed:17576170).<ref>PMID:17576170</ref> <ref>PMID:20176268</ref> <ref>PMID:22158414</ref> <ref>PMID:24600447</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/ar/1ar2_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=1ar2 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+BACKGROUND: Immunoglobulin domains owe a crucial fraction of their conformational stability to an invariant central disulfide bridge, the closure of which requires oxidation. Under the reducing conditions prevailing in cell cytoplasm, accumulation of soluble immunoglobulin is prohibited by its inability to acquire and maintain the native conformation. Previously, we have shown that disulfide-free immunoglobulins can be produced in Escherichia coli and purified from cytoplasmic extracts. RESULTS: Immunoglobulin REIv is the variable domain of a human kappa light chain. The disulfide-free variant REIv-C23V/Y32H was crystallized and its structure analyzed by X-ray crystallography (2.8 A resolution). The conformation of the variant is nearly identical to that of the wild-type protein and the conformationally stabilized variant REIv-T39K. This constitutes the first crystal structure of an immunoglobulin fragment without a disulfide bridge. The lack of the disulfide bridge produces no obvious local change in structure (compared with the wild type), whereas the Y32H mutation allows the formation of an additional hydrogen bond. There is a further change in the structure that is seen in the dimer in which Tyr49 has flipped out of the dimer interface in the mutant. CONCLUSIONS: Immunoglobulin derivatives without a central disulfide bridge but with stringently conserved wild-type conformation can be constructed in a practical two-step approach. First, the protein is endowed with additional folding stability by the introduction of one or more stabilizing amino acid exchanges; second, the disulfide bridge is destroyed by substitution of one of the two invariant cysteines. Such derivatives can be accumulated in soluble form in the cytoplasmic compartment of the E. coli cell. Higher protein yields and evolutionary refinement of catalytic antibodies by genetic complementation are among the possible advantages.
-===DISULFIDE-FREE IMMUNOGLOBULIN FRAGMENT===
+X-ray crystallography reveals stringent conservation of protein fold after removal of the only disulfide bridge from a stabilized immunoglobulin variable domain.,Uson I, Bes MT, Sheldrick GM, Schneider TR, Hartsch T, Fritz HJ Fold Des. 1997;2(6):357-61. PMID:9427009<ref>PMID:9427009</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_9427009}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 1ar2" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 9427009 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_9427009}}
+__TOC__
+</StructureSection>
-==About this Structure==
-AR2 is a [[Single protein]] structure of 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=1AR2 OCA].
-==Reference==
-X-ray crystallography reveals stringent conservation of protein fold after removal of the only disulfide bridge from a stabilized immunoglobulin variable domain., Uson I, Bes MT, Sheldrick GM, Schneider TR, Hartsch T, Fritz HJ, Fold Des. 1997;2(6):357-61. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9427009 9427009]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Bes, M T.]]
+[[Category: Bes MT]]
-[[Category: Fritz, H J.]]
+[[Category: Fritz H-J]]
-[[Category: Hartsch, T.]]
+[[Category: Hartsch T]]
-[[Category: Schneider, T R.]]
+[[Category: Schneider TR]]
-[[Category: Sheldrick, G M.]]
+[[Category: Sheldrick GM]]
-[[Category: Uson, I.]]
+[[Category: Uson I]]
-[[Category: Bence-jone]]
-[[Category: Disulfide-free]]
-[[Category: Immunoglobulin fragment]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 17:26:53 2008''