کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2187596 1096128 2008 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure of Antibody F425-B4e8 in Complex with a V3 Peptide Reveals a New Binding Mode for HIV-1 Neutralization
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Structure of Antibody F425-B4e8 in Complex with a V3 Peptide Reveals a New Binding Mode for HIV-1 Neutralization
چکیده انگلیسی

F425-B4e8 (B4e8) is a monoclonal antibody isolated from a human immunodeficiency virus type 1 (HIV-1)-infected individual that recognizes the V3 variable loop on the gp120 subunit of the viral envelope spike. B4e8 neutralizes a subset of HIV-1 primary isolates from subtypes B, C and D, which places this antibody among the very few human anti-V3 antibodies with notable cross-neutralizing activity. Here, the crystal structure of the B4e8 Fab′ fragment in complex with a 24-mer V3 peptide (RP142) at 2.8 Å resolution is described. The complex structure reveals that the antibody recognizes a novel V3 loop conformation, featuring a five-residue α-turn around the conserved GPGRA apex of the β-hairpin loop. In agreement with previous mutagenesis analyses, the Fab′ interacts primarily with V3 through side-chain contacts with just two residues, IleP309 and ArgP315, while the remaining contacts are to the main chain. The structure helps explain how B4e8 can tolerate a certain degree of sequence variation within V3 and, hence, is able to neutralize an appreciable number of different HIV-1 isolates.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 375, Issue 4, 25 January 2008, Pages 969–978
نویسندگان
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