Recognition properties of V3-specific antibodies to V3 loop peptides derived from HIV-1 gp120 presented in multiple conformations

Citation
Jg. Huisman et al., Recognition properties of V3-specific antibodies to V3 loop peptides derived from HIV-1 gp120 presented in multiple conformations, BIOCHEM, 39(35), 2000, pp. 10866-10876
Citations number
53
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMISTRY
ISSN journal
00062960 → ACNP
Volume
39
Issue
35
Year of publication
2000
Pages
10866 - 10876
Database
ISI
SICI code
0006-2960(20000905)39:35<10866:RPOVAT>2.0.ZU;2-I
Abstract
TO identify structural constraints and amino acid sequences important for a ntibody recognition of the third variable domain (V3) of HIV-1 gp120, we ha ve studied the solution conformation of three 35-mer circular V3 loop pepti des derived from HIV-1 strains which differ in syncytium- (SI) and nonsyncy tium-inducing (NSI) capacity. In addition to 2D NMR and CD analyses, fluid- and solid-phase immunoassays were performed using V3-specific antibodies t o V3 peptides and gp120 derived from different strains of HIV-1. NMR and CD spectroscopy indicated that circular and linear V3 loops exist in water as a dynamic ensemble of multiple conformations. Amino acid substitutions and biochemical modifications of the V3 loop were found to affect antibody bin ding depending on the presentation of the antigens. From NMR observations a nd immunological experiments, we provide evidence for a V3 loop specific mo noclonal antibody interaction which is directed predominantly against linea r epitopes rather than against discontinuous epitopes. The absence of a sin gle defined solution conformation of 35-mer circular V3 peptides should be taken into account when using VS-related peptides to investigate structural elements in the V3 domain of the gp120 envelope protein of HIV-1 involved in biological processes of the virus.