4rqq

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Crystal structure of human Fab PGDM1400, a broadly reactive and potent HIV-1 neutralizing antibody

Structural highlights

4rqq 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.
Method:X-ray diffraction, Resolution 3.1Å
Ligands:TYS
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Broadly neutralizing antibodies (bnAbs) targeting the trimer apex of HIV envelope are favored candidates for vaccine design and immunotherapy because of their great neutralization breadth and potency. However, methods of isolating bnAbs against this site have been limited by the quaternary nature of the epitope region. Here we report the use of a recombinant HIV envelope trimer, BG505 SOSIP.664 gp140, as an affinity reagent to isolate quaternary-dependent bnAbs from the peripheral blood mononuclear cells of a chronically infected donor. The newly isolated bnAbs, named "PGDM1400-1412," show a wide range of neutralization breadth and potency. One of these variants, PGDM1400, is exceptionally broad and potent with cross-clade neutralization coverage of 83% at a median IC50 of 0.003 microg/mL. Overall, our results highlight the utility of BG505 SOSIP.664 gp140 as a tool for the isolation of quaternary-dependent antibodies and reveal a mosaic of antibody responses against the trimer apex within a clonal family.

Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex.,Sok D, van Gils MJ, Pauthner M, Julien JP, Saye-Francisco KL, Hsueh J, Briney B, Lee JH, Le KM, Lee PS, Hua Y, Seaman MS, Moore JP, Ward AB, Wilson IA, Sanders RW, Burton DR Proc Natl Acad Sci U S A. 2014 Nov 24. pii: 201415789. PMID:25422458[1]

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

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References

  1. Sok D, van Gils MJ, Pauthner M, Julien JP, Saye-Francisco KL, Hsueh J, Briney B, Lee JH, Le KM, Lee PS, Hua Y, Seaman MS, Moore JP, Ward AB, Wilson IA, Sanders RW, Burton DR. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. Proc Natl Acad Sci U S A. 2014 Nov 24. pii: 201415789. PMID:25422458 doi:http://dx.doi.org/10.1073/pnas.1415789111

Contents


PDB ID 4rqq

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