3oaz: Difference between revisions
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==A non-self sugar mimic of the HIV glycan shield shows enhanced antigenicity== | |||
<StructureSection load='3oaz' size='340' side='right'caption='[[3oaz]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3oaz]] is a 4 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=3OAZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OAZ FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2M5:METHYL+7-DEOXY-L-GLYCERO-ALPHA-D-MANNO-HEPTOPYRANOSIDE'>2M5</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=3oaz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oaz OCA], [https://pdbe.org/3oaz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oaz RCSB], [https://www.ebi.ac.uk/pdbsum/3oaz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oaz ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Antibody 2G12 uniquely neutralizes a broad range of HIV-1 isolates by binding the high-mannose glycans on the HIV-1 surface glycoprotein, gp120. Antigens that resemble these natural epitopes of 2G12 would be highly desirable components for an HIV-1 vaccine. However, host-produced (self)-carbohydrate motifs have been unsuccessful so far at eliciting 2G12-like antibodies that cross-react with gp120. Based on the surprising observation that 2G12 binds nonproteinaceous monosaccharide D-fructose with higher affinity than D-mannose, we show here that a designed set of nonself, synthetic monosaccharides are potent antigens. When introduced to the terminus of the D1 arm of protein glycans recognized by 2G12, their antigenicity is significantly enhanced. Logical variation of these unnatural sugars pinpointed key modifications, and the molecular basis of this increased antigenicity was elucidated using high-resolution crystallographic analyses. Virus-like particle protein conjugates containing such nonself glycans are bound more tightly by 2G12. As immunogens they elicit higher titers of antibodies than those immunogenic conjugates containing the self D1 glycan motif. These antibodies generated from nonself immunogens also cross-react with this self motif, which is found in the glycan shield, when it is presented in a range of different conjugates and glycans. However, these antibodies did not bind this glycan motif when present on gp120. | |||
A nonself sugar mimic of the HIV glycan shield shows enhanced antigenicity.,Doores KJ, Fulton Z, Hong V, Patel MK, Scanlan CN, Wormald MR, Finn MG, Burton DR, Wilson IA, Davis BG Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17107-12. Epub 2010 Sep 17. PMID:20852065<ref>PMID:20852065</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3oaz" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Sandbox 20009|Sandbox 20009]] | |||
*[[3D structures of human antibody|3D structures of human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Burton DR]] | |||
[[Category: Davis BG]] | |||
[[Category: Doores KJ]] | |||
[[Category: Finn MG]] | |||
[[Category: Fulton Z]] | |||
[[Category: Hong V]] | |||
[[Category: Patel MK]] | |||
[[Category: Scanlan CN]] | |||
[[Category: Wilson IA]] | |||
[[Category: Wormald MR]] | |||
Latest revision as of 12:32, 6 September 2023
A non-self sugar mimic of the HIV glycan shield shows enhanced antigenicityA non-self sugar mimic of the HIV glycan shield shows enhanced antigenicity
Structural highlights
Publication Abstract from PubMedAntibody 2G12 uniquely neutralizes a broad range of HIV-1 isolates by binding the high-mannose glycans on the HIV-1 surface glycoprotein, gp120. Antigens that resemble these natural epitopes of 2G12 would be highly desirable components for an HIV-1 vaccine. However, host-produced (self)-carbohydrate motifs have been unsuccessful so far at eliciting 2G12-like antibodies that cross-react with gp120. Based on the surprising observation that 2G12 binds nonproteinaceous monosaccharide D-fructose with higher affinity than D-mannose, we show here that a designed set of nonself, synthetic monosaccharides are potent antigens. When introduced to the terminus of the D1 arm of protein glycans recognized by 2G12, their antigenicity is significantly enhanced. Logical variation of these unnatural sugars pinpointed key modifications, and the molecular basis of this increased antigenicity was elucidated using high-resolution crystallographic analyses. Virus-like particle protein conjugates containing such nonself glycans are bound more tightly by 2G12. As immunogens they elicit higher titers of antibodies than those immunogenic conjugates containing the self D1 glycan motif. These antibodies generated from nonself immunogens also cross-react with this self motif, which is found in the glycan shield, when it is presented in a range of different conjugates and glycans. However, these antibodies did not bind this glycan motif when present on gp120. A nonself sugar mimic of the HIV glycan shield shows enhanced antigenicity.,Doores KJ, Fulton Z, Hong V, Patel MK, Scanlan CN, Wormald MR, Finn MG, Burton DR, Wilson IA, Davis BG Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17107-12. Epub 2010 Sep 17. PMID:20852065[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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