3eyf: Difference between revisions

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{{STRUCTURE_3eyf|  PDB=3eyf  |  SCENE=  }}
==Crystal structure of anti-human cytomegalovirus antibody 8f9 plus gB peptide==
===Crystal structure of anti-human cytomegalovirus antibody 8f9 plus gB peptide===
<StructureSection load='3eyf' size='340' side='right' caption='[[3eyf]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
{{ABSTRACT_PUBMED_18772881}}
== Structural highlights ==
<table><tr><td colspan='2'>[[3eyf]] is a 6 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=3EYF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EYF 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></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3eyo|3eyo]], [[3eyq|3eyq]], [[3f12|3f12]]</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=3eyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eyf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3eyf RCSB], [http://www.ebi.ac.uk/pdbsum/3eyf PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Immunoglobulin genes are generated somatically through specialized mechanisms resulting in a vast repertoire of antigen-binding sites. Despite the stochastic nature of these processes, the V-genes that encode most of the antigen-combining site are under positive evolutionary selection, raising the possibility that V-genes have been selected to encode key structural features of binding sites of protective antibodies against certain pathogens. Human, neutralizing antibodies to human cytomegalovirus that bind the AD-2S1 epitope on its gB envelope protein repeatedly use a pair of well-conserved, germline V-genes IGHV3-30 and IGKV3-11. Here, we present crystallographic, kinetic and thermodynamic analyses of the binding site of such an antibody and that of its primary immunoglobulin ancestor. These show that these germline V-genes encode key side chain contacts with the viral antigen and thereby dictate key structural features of the hypermutated, high-affinity neutralizing antibody. V-genes may thus encode an innate, protective immunological memory that targets vulnerable, invariant sites on multiple pathogens.


==Function==
Germline V-genes sculpt the binding site of a family of antibodies neutralizing human cytomegalovirus.,Thomson CA, Bryson S, McLean GR, Creagh AL, Pai EF, Schrader JW EMBO J. 2008 Oct 8;27(19):2592-602. Epub 2008 Sep 4. PMID:18772881<ref>PMID:18772881</ref>
[[http://www.uniprot.org/uniprot/VGLB_HCMVT VGLB_HCMVT]] Envelope glycoprotein that plays a role in host cell entry, cell to-cell virus transmission, and fusion of infected cells. May be involved in the initial attachment via binding to heparan sulfate together with the gM/gN complex that binds heparin with higher affinity. Interacts with host integrin ITGB1, PDGFRA and EGFR that likely serve as postattachment entry receptors. Participates also in the fusion of viral and cellular membranes leading to virus entry into the host cell. Membrane fusion is mediated by the fusion machinery composed at least of gB and the heterodimer gH/gL (By similarity).  Viral ligand for CD209/DC-SIGN. This interaction allows capture of viral particles by dendritic (DCs) cells and subsequent virus transmission to permissive cells. DCs are professional antigen presenting cells, critical for host immunity by inducing specific immune responses against a broad variety of pathogens. They act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. CMV subverts the migration properties of dendritic cells to gain access to target organs or susceptible cells.  


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[3eyf]] is a 6 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=3EYF OCA].
</div>


==See Also==
==See Also==
*[[Antibody|Antibody]]
*[[Antibody|Antibody]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:018772881</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Bryson, S.]]
[[Category: Bryson, S]]
[[Category: Creagh, A L.]]
[[Category: Creagh, A L]]
[[Category: McLean, G R.]]
[[Category: McLean, G R]]
[[Category: Pai, E F.]]
[[Category: Pai, E F]]
[[Category: Schrader, J W.]]
[[Category: Schrader, J W]]
[[Category: Thomson, C A.]]
[[Category: Thomson, C A]]
[[Category: Antibody]]
[[Category: Antibody]]
[[Category: Cleavage on pair of basic residue]]
[[Category: Cleavage on pair of basic residue]]

Revision as of 16:30, 18 December 2014

Crystal structure of anti-human cytomegalovirus antibody 8f9 plus gB peptideCrystal structure of anti-human cytomegalovirus antibody 8f9 plus gB peptide

Structural highlights

3eyf is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Resources:FirstGlance, OCA, RCSB, PDBsum

Publication Abstract from PubMed

Immunoglobulin genes are generated somatically through specialized mechanisms resulting in a vast repertoire of antigen-binding sites. Despite the stochastic nature of these processes, the V-genes that encode most of the antigen-combining site are under positive evolutionary selection, raising the possibility that V-genes have been selected to encode key structural features of binding sites of protective antibodies against certain pathogens. Human, neutralizing antibodies to human cytomegalovirus that bind the AD-2S1 epitope on its gB envelope protein repeatedly use a pair of well-conserved, germline V-genes IGHV3-30 and IGKV3-11. Here, we present crystallographic, kinetic and thermodynamic analyses of the binding site of such an antibody and that of its primary immunoglobulin ancestor. These show that these germline V-genes encode key side chain contacts with the viral antigen and thereby dictate key structural features of the hypermutated, high-affinity neutralizing antibody. V-genes may thus encode an innate, protective immunological memory that targets vulnerable, invariant sites on multiple pathogens.

Germline V-genes sculpt the binding site of a family of antibodies neutralizing human cytomegalovirus.,Thomson CA, Bryson S, McLean GR, Creagh AL, Pai EF, Schrader JW EMBO J. 2008 Oct 8;27(19):2592-602. Epub 2008 Sep 4. PMID:18772881[1]

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

See Also

References

  1. Thomson CA, Bryson S, McLean GR, Creagh AL, Pai EF, Schrader JW. Germline V-genes sculpt the binding site of a family of antibodies neutralizing human cytomegalovirus. EMBO J. 2008 Oct 8;27(19):2592-602. Epub 2008 Sep 4. PMID:18772881 doi:10.1038/emboj.2008.179

3eyf, resolution 2.30Å

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