4ob5: Difference between revisions

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-'''Unreleased structure'''
+==Ontogeny of recognition specificity and functionality for the broadly neutralizing anti-HIV antibody 4E10==
+<StructureSection load='4ob5' size='340' side='right' caption='[[4ob5]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4ob5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OB5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OB5 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TMO:TRIMETHYLAMINE+OXIDE'>TMO</scene></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=4ob5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ob5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ob5 RCSB], [http://www.ebi.ac.uk/pdbsum/4ob5 PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The process of antibody ontogeny typically improves affinity, on-rate, and thermostability, narrows polyspecificity, and rigidifies the combining site to the conformer optimal for binding from the broader ensemble accessible to the precursor. However, many broadly-neutralizing anti-HIV antibodies incorporate unusual structural elements and recognition specificities or properties that often lead to autoreactivity. The ontogeny of 4E10, an autoreactive antibody with unexpected combining site flexibility, was delineated through structural and biophysical comparisons of the mature antibody with multiple potential precursors. 4E10 gained affinity primarily by off-rate enhancement through a small number of mutations to a highly conserved recognition surface. Controverting the conventional paradigm, the combining site gained flexibility and autoreactivity during ontogeny, while losing thermostability, though polyspecificity was unaffected. Details of the recognition mechanism, including inferred global effects due to 4E10 binding, suggest that neutralization by 4E10 may involve mechanisms beyond simply binding, also requiring the ability of the antibody to induce conformational changes distant from its binding site. 4E10 is, therefore, unlikely to be re-elicited by conventional vaccination strategies.
-The entry 4ob5 is ON HOLD  until Paper Publication
+Ontogeny of Recognition Specificity and Functionality for the Broadly Neutralizing Anti-HIV Antibody 4E10.,Finton KA, Friend D, Jaffe J, Gewe M, Holmes MA, Larman HB, Stuart A, Larimore K, Greenberg PD, Elledge SJ, Stamatatos L, Strong RK PLoS Pathog. 2014 Sep 25;10(9):e1004403. doi: 10.1371/journal.ppat.1004403., eCollection 2014 Sep. PMID:25254371<ref>PMID:25254371</ref>
-Authors: Jaffe, J.B., Rupert, P.B.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Ontogeny of recognition specificity and functionality for the broadly neutralizing anti-HIV antibody 4E10
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Jaffe, J B.]]
+[[Category: Rupert, P B.]]
+[[Category: Anti-hiv antibody germline precursor]]
+[[Category: Hiv gp41]]
+[[Category: Immune system]]
+[[Category: Immunoglobulin fold]]