4m8q

From Proteopedia

(Difference between revisions)

Current revision

Ontogeny of recognition specificity and functionality for the anti-HIV neutralizing antibody 4E10

Structural highlights

4m8q is a 6 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.89Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KV320_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:17576170, PubMed:20176268).^[1] ^[2] ^[3] ^[4]

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.

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^[5]

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

References

↑ Teng G, Papavasiliou FN. Immunoglobulin somatic hypermutation. Annu Rev Genet. 2007;41:107-20. PMID:17576170 doi:http://dx.doi.org/10.1146/annurev.genet.41.110306.130340
↑ Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S41-52. doi:, 10.1016/j.jaci.2009.09.046. PMID:20176268 doi:http://dx.doi.org/10.1016/j.jaci.2009.09.046
↑ McHeyzer-Williams M, Okitsu S, Wang N, McHeyzer-Williams L. Molecular programming of B cell memory. Nat Rev Immunol. 2011 Dec 9;12(1):24-34. doi: 10.1038/nri3128. PMID:22158414 doi:http://dx.doi.org/10.1038/nri3128
↑ Lefranc MP. Immunoglobulin and T Cell Receptor Genes: IMGT((R)) and the Birth and Rise of Immunoinformatics. Front Immunol. 2014 Feb 5;5:22. doi: 10.3389/fimmu.2014.00022. eCollection 2014. PMID:24600447 doi:http://dx.doi.org/10.3389/fimmu.2014.00022
↑ Finton KA, Friend D, Jaffe J, Gewe M, Holmes MA, Larman HB, Stuart A, Larimore K, Greenberg PD, Elledge SJ, Stamatatos L, Strong RK. Ontogeny of Recognition Specificity and Functionality for the Broadly Neutralizing Anti-HIV Antibody 4E10. PLoS Pathog. 2014 Sep 25;10(9):e1004403. doi: 10.1371/journal.ppat.1004403., eCollection 2014 Sep. PMID:25254371 doi:http://dx.doi.org/10.1371/journal.ppat.1004403

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4m8q"

Categories: Homo sapiens | Large Structures | Synthetic construct | Finton KAK

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4m8q]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M8Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M8Q FirstGlance]. <br>
-</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=4m8q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m8q OCA], [https://pdbe.org/4m8q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m8q RCSB], [https://www.ebi.ac.uk/pdbsum/4m8q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m8q ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.89&#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=4m8q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m8q OCA], [https://pdbe.org/4m8q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m8q RCSB], [https://www.ebi.ac.uk/pdbsum/4m8q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m8q ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/KV320_HUMAN KV320_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>
+[https://www.uniprot.org/uniprot/KV320_HUMAN KV320_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:17576170, PubMed:20176268).<ref>PMID:17576170</ref> <ref>PMID:20176268</ref> <ref>PMID:22158414</ref> <ref>PMID:24600447</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4m8q

From Proteopedia

Current revision

Ontogeny of recognition specificity and functionality for the anti-HIV neutralizing antibody 4E10

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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