Structural highlights
Publication Abstract from PubMedAntibody-Framework-to-Antigen Distance (AFAD) - the distance between the body of an antibody and a protein antigen - is an important parameter governing antibody recognition. Here, we quantify AFAD for ~2,000 non-redundant antibody-protein-antigen complexes in the Protein Data Bank. AFADs showed a gaussian distribution with mean of 16.3 A and standard deviation (sigma) of 2.4 A. Notably, antibody-antigen complexes with extended AFADs (>3sigma) were exclusively human immunodeficiency virus-type 1 (HIV-1)-neutralizing antibodies. High correlation (R(2) = 0.8110) was observed between AFADs and glycan coverage, as assessed by molecular dynamics simulations of the HIV-1-envelope trimer. Especially long AFADs were observed for antibodies targeting the glycosylated trimer apex, and we tested the impact of introducing an apex-glycan hole (N160K); the cryo-EM structure of the glycan hole-targeting HIV-1-neutralizing antibody 2909 in complex with an N160K-envelope trimer revealed a substantially shorter AFAD. Overall, extended AFADs exclusively recognized densely glycosylated surfaces, with the introduction of a glycan hole enabling closer recognition. Extended antibody-framework-to-antigen distance observed exclusively with broad HIV-1-neutralizing antibodies recognizing glycan-dense surfaces.,Lee M, Changela A, Gorman J, Rawi R, Bylund T, Chao CW, Lin BC, Louder MK, Olia AS, Zhang B, Doria-Rose NA, Zolla-Pazner S, Shapiro L, Chuang GY, Kwong PD Nat Commun. 2021 Nov 9;12(1):6470. doi: 10.1038/s41467-021-26579-z. PMID:34753907[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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