6p8m: Difference between revisions
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==Crystal Structure of Antibody P-p3b3 A60C Heavy Chain in Complex with 426c HIV-1 gp120 core G459C== | |||
<StructureSection load='6p8m' size='340' side='right'caption='[[6p8m]], [[Resolution|resolution]] 3.59Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6p8m]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P8M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P8M 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]] 3.594Å</td></tr> | |||
<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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=6p8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p8m OCA], [https://pdbe.org/6p8m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p8m RCSB], [https://www.ebi.ac.uk/pdbsum/6p8m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p8m ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/M4Q8P8_9HIV1 M4Q8P8_9HIV1] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Broadly HIV-1 neutralizing VRC01 class antibodies target the CD4-binding site of Env. They are derived from VH1-2( *)02 antibody heavy chains paired with rare light chains expressing 5-amino acid-long CDRL3s. They have been isolated from infected subjects but have not yet been elicited by immunization. Env-derived immunogens capable of binding the germline forms of VRC01 B cell receptors on naive B cells have been designed and evaluated in knockin mice. However, the elicited antibodies cannot bypass glycans present on the conserved position N276 of Env, which restricts access to the CD4-binding site. Efforts to guide the appropriate maturation of these antibodies by sequential immunization have not yet been successful. Here, we report on a two-step immunization scheme that leads to the maturation of VRC01-like antibodies capable of accommodating the N276 glycan and displaying autologous tier 2 neutralizing activities. Our results are relevant to clinical trials aiming to elicit VRC01 antibodies. | |||
Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization.,Parks KR, MacCamy AJ, Trichka J, Gray M, Weidle C, Borst AJ, Khechaduri A, Takushi B, Agrawal P, Guenaga J, Wyatt RT, Coler R, Seaman M, LaBranche C, Montefiori DC, Veesler D, Pancera M, McGuire A, Stamatatos L Cell Rep. 2019 Dec 3;29(10):3060-3072.e7. doi: 10.1016/j.celrep.2019.10.071. PMID:31801073<ref>PMID:31801073</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6p8m" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Gp120 3D structures|Gp120 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human immunodeficiency virus 1]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Pancera M]] | |||
[[Category: Weidle C]] | |||
Latest revision as of 10:25, 11 October 2023
Crystal Structure of Antibody P-p3b3 A60C Heavy Chain in Complex with 426c HIV-1 gp120 core G459CCrystal Structure of Antibody P-p3b3 A60C Heavy Chain in Complex with 426c HIV-1 gp120 core G459C
Structural highlights
FunctionPublication Abstract from PubMedBroadly HIV-1 neutralizing VRC01 class antibodies target the CD4-binding site of Env. They are derived from VH1-2( *)02 antibody heavy chains paired with rare light chains expressing 5-amino acid-long CDRL3s. They have been isolated from infected subjects but have not yet been elicited by immunization. Env-derived immunogens capable of binding the germline forms of VRC01 B cell receptors on naive B cells have been designed and evaluated in knockin mice. However, the elicited antibodies cannot bypass glycans present on the conserved position N276 of Env, which restricts access to the CD4-binding site. Efforts to guide the appropriate maturation of these antibodies by sequential immunization have not yet been successful. Here, we report on a two-step immunization scheme that leads to the maturation of VRC01-like antibodies capable of accommodating the N276 glycan and displaying autologous tier 2 neutralizing activities. Our results are relevant to clinical trials aiming to elicit VRC01 antibodies. Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization.,Parks KR, MacCamy AJ, Trichka J, Gray M, Weidle C, Borst AJ, Khechaduri A, Takushi B, Agrawal P, Guenaga J, Wyatt RT, Coler R, Seaman M, LaBranche C, Montefiori DC, Veesler D, Pancera M, McGuire A, Stamatatos L Cell Rep. 2019 Dec 3;29(10):3060-3072.e7. doi: 10.1016/j.celrep.2019.10.071. PMID:31801073[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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