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6apd

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Crystal structure of RSV F bound by AM22 and the infant antibody ADI-19425

Structural highlights

6apd is a 15 chain structure with sequence from Bpt4 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	IGH@ (HUMAN), IGHV3-21 (HUMAN), IGL@ (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HV321_HUMAN] V region of the variable domain of immunoglobulin heavy 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:22158414, PubMed:20176268). 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).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Respiratory syncytial virus (RSV) is a leading cause of infant mortality, and there are currently no licensed vaccines to protect this vulnerable population. A comprehensive understanding of infant antibody responses to natural RSV infection would facilitate vaccine development. Here, we isolated more than 450 RSV fusion glycoprotein (F)-specific antibodies from 7 RSV-infected infants and found that half of the antibodies recognized only two antigenic sites. Antibodies targeting both sites showed convergent sequence features, and structural studies revealed the molecular basis for their recognition of RSV F. A subset of antibodies targeting one of these sites displayed potent neutralizing activity despite lacking somatic mutations, and similar antibodies were detected in RSV-naive B cell repertoires, suggesting that expansion of these B cells in infants may be possible with suitably designed vaccine antigens. Collectively, our results provide fundamental insights into infant antibody responses and a framework for the rational design of age-specific RSV vaccines.

Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation.,Goodwin E, Gilman MSA, Wrapp D, Chen M, Ngwuta JO, Moin SM, Bai P, Sivasubramanian A, Connor RI, Wright PF, Graham BS, McLellan JS, Walker LM Immunity. 2018 Feb 20;48(2):339-349.e5. doi: 10.1016/j.immuni.2018.01.005. Epub, 2018 Feb 3. PMID:29396163^[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
↑ Goodwin E, Gilman MSA, Wrapp D, Chen M, Ngwuta JO, Moin SM, Bai P, Sivasubramanian A, Connor RI, Wright PF, Graham BS, McLellan JS, Walker LM. Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation. Immunity. 2018 Feb 20;48(2):339-349.e5. doi: 10.1016/j.immuni.2018.01.005. Epub, 2018 Feb 3. PMID:29396163 doi:http://dx.doi.org/10.1016/j.immuni.2018.01.005

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/6apd"

@@ Line 1: / Line 1: @@
 ==Crystal structure of RSV F bound by AM22 and the infant antibody ADI-19425==
-<StructureSection load='6apd' size='340' side='right' caption='[[6apd]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
+<StructureSection load='6apd' size='340' side='right'caption='[[6apd]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6apd]] is a 15 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6APD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6APD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6apd]] is a 15 chain structure with sequence from [http://en.wikipedia.org/wiki/Bpt4 Bpt4] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6APD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6APD FirstGlance]. <br>
-</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=6apd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6apd OCA], [http://pdbe.org/6apd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6apd RCSB], [http://www.ebi.ac.uk/pdbsum/6apd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6apd ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGH@ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IGHV3-21 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IGL@ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6apd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6apd OCA], [http://pdbe.org/6apd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6apd RCSB], [http://www.ebi.ac.uk/pdbsum/6apd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6apd ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Bpt4]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: McLellan, J S]]
 [[Category: Wrapp, D]]

6apd

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Current revision

Crystal structure of RSV F bound by AM22 and the infant antibody ADI-19425

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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