Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9
By J. McLellan, M. Pancera, Chris Carrico, J. Gorman, J. Julien, R. Khayat, R. Louder, R. Pejchal, M. Sastry, K. Dai and 37 more. Nature, 2011
852 citations recorded by the source corpus.
Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded β-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which—with PG9—involves a site of vulnerability comprising just two glycans and a strand.
Subfields: Molecular Biology, Radiology, Nuclear Medicine and Imaging, Virology
View Paper: https://www.semanticscholar.org/paper/5d83efe463e1b66414b96ec3928cc343864c824d
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In Radiology, Nuclear Medicine and Imaging
Citations in the corpus
- Biological roles of glycans (2016, background): “Sometimes, such protective glycosylation can become so dense that it generates unique clustered epitopes recognized by specific antibodies, such as that seen on the surface of the HIV virion (507) (508) (509) 594) .”
- Crystal structure of a soluble cleaved HIV-1 envelope trimer (2013, background): “Antibody interactions additional to those previously described in the PG9/PG16-V1/V2-scaffold co-crystal structures (4, 6) are predicted to occur with gp120 V3, as well as with residues N160 and N197 of the adjacent protomer.”
- Design of Nanoparticulate Group 2 Influenza Virus Hemagglutinin Stem Antigens That Activate Unmutated Ancestor B Cell Receptors of Broadly Neutralizing Antibody Lineages (2018, neutral): “Eukaryotic expression of HA stem immunogens may be of particular importance because each native HA stem trimer has nine glycans and glycans have been observed to guide antibody binding by either masking certain epitopes (58, 59) or participating as part of an epitope surface (60).”
- Neutralization of influenza A viruses by insertion of a single antibody loop into the receptor binding site (2012, neutral): “In this analysis, residues are considered conserved if substitutions are restricted to other amino acids in the same group: (1) Asp, Asn, Glu, Gln (negatively charged or isosteric polar substitutions); (2) Val, Ile, Leu, Met (small hydrophobic); (3) Phe and Tyr (aromatic); and (4) Ser and Thr (small”
- Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles (2016, neutral): “Our results demonstrate that the V1V2 region of HIV-1 Env can be presented in a native-like trimeric conformation on FR nanoparticle.”