3mme: Difference between revisions
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==Structure and functional dissection of PG16, an antibody with broad and potent neutralization of HIV-1== | ==Structure and functional dissection of PG16, an antibody with broad and potent neutralization of HIV-1== | ||
<StructureSection load='3mme' size='340' side='right' caption='[[3mme]], [[Resolution|resolution]] 3.97Å' scene=''> | <StructureSection load='3mme' size='340' side='right'caption='[[3mme]], [[Resolution|resolution]] 3.97Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3mme]] is a 6 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3mme]] is a 6 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=3MME OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MME FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.97Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3mme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mme OCA], [https://pdbe.org/3mme PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mme RCSB], [https://www.ebi.ac.uk/pdbsum/3mme PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mme ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mm/3mme_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mm/3mme_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
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==See Also== | ==See Also== | ||
*[[3D structures of antibody|3D structures of antibody]] | *[[Antibody 3D structures|Antibody 3D structures]] | ||
*[[Sandbox 20009|Sandbox 20009]] | |||
*[[3D structures of human antibody|3D structures of human antibody]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Kwong | [[Category: Large Structures]] | ||
[[Category: McLellan | [[Category: Kwong P]] | ||
[[Category: Pancera | [[Category: McLellan J]] | ||
[[Category: Zhou | [[Category: Pancera M]] | ||
[[Category: Zhu | [[Category: Zhou T]] | ||
[[Category: Zhu J]] | |||
Latest revision as of 09:29, 27 November 2024
Structure and functional dissection of PG16, an antibody with broad and potent neutralization of HIV-1Structure and functional dissection of PG16, an antibody with broad and potent neutralization of HIV-1
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 resists neutralization by most antibodies. Two somatically related human antibodies, PG9 and PG16, however, each neutralize 70 to 80% of circulating HIV-1 isolates. Here we present the structure of the antigen-binding fragment of PG16 in monoclinic and orthorhombic lattices at 2.4 and 4.0 A, respectively, and use a combination of structural analysis, paratope dissection, and neutralization assessment to determine the functional relevance of three unusual PG9/PG16 features: N-linked glycosylation, extensive affinity maturation, and a heavy chain-third complementarity-determining region (CDR H3) that is one of the longest observed in human antibodies. Glycosylation extended off the side of the light chain variable domain and was not required for neutralization. The CDR H3 formed an axe-shaped subdomain, which comprised 42% of the CDR surface, with the axe head looming approximately 20 A above the other combining loops. Comprehensive sets of chimeric swaps between PG9 and PG16 of light chain, heavy chain, and CDR H3 were employed to decipher structure-function relationships. Chimeric swaps generally complemented functionally, with differences in PG9/PG16 neutralization related primarily to residue differences in CDR H3. Meanwhile, chimeric reversions to genomic V genes showed isolate-dependent effects, with affinity maturation playing a significant role in augmenting neutralization breadth (P = 0.036) and potency (P < 0.0001). The structural and functional details of extraordinary CDR H3 and extensive affinity maturation provide insights into the neutralization mechanism of and the elicitation pathway for broadly neutralizing antibodies like PG9 and PG16. Crystal structure of PG16 and chimeric dissection with somatically related PG9: structure-function analysis of two quaternary-specific antibodies that effectively neutralize HIV-1.,Pancera M, McLellan JS, Wu X, Zhu J, Changela A, Schmidt SD, Yang Y, Zhou T, Phogat S, Mascola JR, Kwong PD J Virol. 2010 Aug;84(16):8098-110. Epub 2010 Jun 10. PMID:20538861[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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