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215 a.a.
211 a.a.
15 a.a.
_CL
_ZN
Key reference
DOI no: 10.1016/j.jmb.2007.11.013 J Mol Biol 375:969-978 (2008) PubMed id: 18068724
Structure of antibody F425-B4e8 in complex with a V3 peptide reveals a new binding mode for HIV-1 neutralization. C.H.Bell, R.Pantophlet, A.Schiefner, L.A.Cavacini, R.L.Stanfield, D.R.Burton, I.A.Wilson. ABSTRACT
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 A resolution is described. The complex structure reveals that the antibody recognizes a novel V3 loop conformation, featuring a five-residue alpha-turn around the conserved GPGRA apex of the beta-hairpin loop. In agreement with previous mutagenesis analyses, the Fab' interacts primarily with V3 through side-chain contacts with just two residues, Ile(P309) and Arg(P315), 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.
Literature references that cite this PDB file's key reference
PubMed id Reference
19073717 J.Takehisa, M.H.Kraus, A.Ayouba, E.Bailes, F.Van Heuverswyn, J.M.Decker, Y.Li, R.S.Rudicell, G.H.Learn, C.Neel, E.M.Ngole, G.M.Shaw, M.Peeters, P.M.Sharp, and B.H.Hahn (2009).
Origin and biology of simian immunodeficiency virus in wild-living western gorillas.J Virol, 83, 1635-1648.
19019969 K.L.Davis, F.Bibollet-Ruche, H.Li, J.M.Decker, O.Kutsch, L.Morris, A.Salomon, A.Pinter, J.A.Hoxie, B.H.Hahn, P.D.Kwong, and G.M.Shaw (2009).
Human immunodeficiency virus type 2 (HIV-2)/HIV-1 envelope chimeras detect high titers of broadly reactive HIV-1 V3-specific antibodies in human plasma.J Virol, 83, 1240-1259.
19404249 P.C.Doherty, and S.J.Turner (2009).
Thinking about broadly cross-reactive vaccines.Clin Pharmacol Ther, 85, 665-668.
19448659 P.D.Kwong, and I.A.Wilson (2009).
HIV-1 and influenza antibodies: seeing antigens in new ways.Nat Immunol, 10, 573-578.
19680536 R.Berro, R.W.Sanders, M.Lu, P.J.Klasse, and J.P.Moore (2009).
Two HIV-1 variants resistant to small molecule CCR5 inhibitors differ in how they use CCR5 for entry.PLoS Pathog, 5, e1000548.
19036813 R.Pantophlet, M.Wang, R.O.Aguilar-Sino, and D.R.Burton (2009).
The human immunodeficiency virus type 1 envelope spike of primary viruses can suppress antibody access to variable regions.J Virol, 83, 1649-1659. 18638381 M.L.Visciano, M.Tuen, P.D.Chen, and C.E.Hioe (2008).
Antibodies to the CD4-binding site of HIV-1 gp120 suppress gp120-specific CD4 T cell response while enhancing antibody response.Infect Agent Cancer, 3, 11.
18495775 M.Vaine, S.Wang, E.T.Crooks, P.Jiang, D.C.Montefiori, J.Binley, and S.Lu (2008).
Improved induction of antibodies against key neutralizing epitopes by human immunodeficiency virus type 1 gp120 DNA prime-protein boost vaccination compared to gp120 protein-only vaccination.J Virol, 82, 7369-7378. The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.
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