2xa3: Difference between revisions
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< | ==crystal structure of the broadly neutralizing llama VHH D7 and its mode of HIV-1 gp120 interaction== | ||
<StructureSection load='2xa3' size='340' side='right'caption='[[2xa3]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2xa3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XA3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XA3 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]] 1.5Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2xa3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xa3 OCA], [https://pdbe.org/2xa3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xa3 RCSB], [https://www.ebi.ac.uk/pdbsum/2xa3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xa3 ProSAT]</span></td></tr> | |||
</table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xa/2xa3_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2xa3 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
HIV-1 entry into host cells is mediated by the sequential binding of the envelope glycoprotein gp120 to CD4 and a chemokine receptor. Antibodies binding to epitopes overlapping the CD4-binding site on gp120 are potent inhibitors of HIV entry, such as the llama heavy chain antibody fragment V(HH) D7, which has cross-clade neutralizing properties and competes with CD4 and mAb b12 for high affinity binding to gp120. We report the crystal structure of the D7 V(HH) at 1.5 A resolution, which reveals the molecular details of the complementarity determining regions (CDR) and substantial flexibility of CDR3 that could facilitate an induced fit interaction with gp120. Structural comparison of CDRs from other CD4 binding site antibodies suggests diverse modes of interaction. Mutational analysis identified CDR3 as a key component of gp120 interaction as determined by surface plasmon resonance. A decrease in affinity is directly coupled to the neutralization efficiency since mutations that decrease gp120 interaction increase the IC50 required for HIV-1 IIIB neutralization. Thus the structural study identifies the long CDR3 of D7 as the key determinant of interaction and HIV-1 neutralization. Furthermore, our data confirm that the structural plasticity of gp120 can accommodate multiple modes of antibody binding within the CD4 binding site. | |||
Crystal Structure of the Neutralizing Llama V(HH) D7 and Its Mode of HIV-1 gp120 Interaction.,Hinz A, Lutje Hulsik D, Forsman A, Koh WW, Belrhali H, Gorlani A, de Haard H, Weiss RA, Verrips T, Weissenhorn W PLoS One. 2010 May 5;5(5):e10482. PMID:20463957<ref>PMID:20463957</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2xa3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
== | </StructureSection> | ||
[[ | |||
== | |||
< | |||
[[Category: Lama glama]] | [[Category: Lama glama]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Belrhali H]] | ||
[[Category: Forsman | [[Category: Forsman A]] | ||
[[Category: Gorlani | [[Category: Gorlani A]] | ||
[[Category: Hinz | [[Category: Hinz A]] | ||
[[Category: Koh | [[Category: Koh W]] | ||
[[Category: | [[Category: Lutje Hulsik D]] | ||
[[Category: Verrips | [[Category: Verrips T]] | ||
[[Category: Weiss | [[Category: Weiss RA]] | ||
[[Category: Weissenhorn | [[Category: Weissenhorn W]] | ||
[[Category: | [[Category: De Haard H]] | ||
Latest revision as of 13:27, 20 December 2023
crystal structure of the broadly neutralizing llama VHH D7 and its mode of HIV-1 gp120 interactioncrystal structure of the broadly neutralizing llama VHH D7 and its mode of HIV-1 gp120 interaction
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHIV-1 entry into host cells is mediated by the sequential binding of the envelope glycoprotein gp120 to CD4 and a chemokine receptor. Antibodies binding to epitopes overlapping the CD4-binding site on gp120 are potent inhibitors of HIV entry, such as the llama heavy chain antibody fragment V(HH) D7, which has cross-clade neutralizing properties and competes with CD4 and mAb b12 for high affinity binding to gp120. We report the crystal structure of the D7 V(HH) at 1.5 A resolution, which reveals the molecular details of the complementarity determining regions (CDR) and substantial flexibility of CDR3 that could facilitate an induced fit interaction with gp120. Structural comparison of CDRs from other CD4 binding site antibodies suggests diverse modes of interaction. Mutational analysis identified CDR3 as a key component of gp120 interaction as determined by surface plasmon resonance. A decrease in affinity is directly coupled to the neutralization efficiency since mutations that decrease gp120 interaction increase the IC50 required for HIV-1 IIIB neutralization. Thus the structural study identifies the long CDR3 of D7 as the key determinant of interaction and HIV-1 neutralization. Furthermore, our data confirm that the structural plasticity of gp120 can accommodate multiple modes of antibody binding within the CD4 binding site. Crystal Structure of the Neutralizing Llama V(HH) D7 and Its Mode of HIV-1 gp120 Interaction.,Hinz A, Lutje Hulsik D, Forsman A, Koh WW, Belrhali H, Gorlani A, de Haard H, Weiss RA, Verrips T, Weissenhorn W PLoS One. 2010 May 5;5(5):e10482. PMID:20463957[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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