Title
Recognition properties of V3-specific antibodies to V3 loop peptides derived from HIV-1 gp120 presented in multiple conformations
Author
TNO Preventie en Gezondheid
Huisman, J.G.
Carotenuto, A.
Labrijn, A.F.
Papavoine, C.H.M.
Laman, J.D.
Schellekens, M.M.
Koppelman, M.H.G.M.
Hilbers, C.W.
Publication year
2000
Abstract
To identify structural constraints and amino acid sequences important for antibody recognition of the third variable domain (V3) of HIV-1 gp120, we have studied the solution conformation of three 35-mer circular V3 loop peptides derived from HIV-1 strains which differ in syncytium- (SI) and non-syncytium-inducing (NSI) capacity. In addition to 2D NMR and CD analyses, fluid- and solid-phase immunoassays were performed using V3-specific antibodies to 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 binding depending on the presentation of the antigens. From NMR observations and immunological experiments, we provide evidence for a V3 loop specific monoclonal antibody interaction which is directed predominantly against linear epitopes rather than against discontinuous epitopes. The absence of a single defined solution conformation of 35-mer circular V3 peptides should be taken into account when using V3-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. Chemicals / CAS HIV Antibodies; HIV Antigens; HIV Envelope Protein gp120; Peptide Fragments; Thrombin, 3.4.21.5; Water, 7732-18-5.
Subject
glycoprotein gp 120
amino acid sequence
amino acid substitution
antigen recognition
circular dichroism
Human immunodeficiency virus 1
nonhuman
nuclear magnetic resonance spectroscopy
priority journal
protein analysis
protein conformation
protein modification
structure analysis
Amino Acid Sequence
Antibody Specificity
Antigen Presentation
Antigen-Antibody Reactions
Circular Dichroism
Enzyme-Linked Immunosorbent Assay
Giant Cells
HIV Antibodies
HIV Antigens
HIV Envelope Protein gp120
HIV-1
Hydrolysis
Methylation
Molecular Sequence Data
Nuclear Magnetic Resonance, Biomolecular
Oxidation-Reduction
Peptide Fragments
Phenotype
Protein Conformation
Protein Denaturation
Radioimmunoassay
Thermodynamics
Thrombin
Water
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DOI
https://doi.org/10.1021/bi0004504
TNO identifier
953477
ISSN
0006-2960
Source
Biochemistry, 39 (39), 10866-10876
Document type
article