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Selected Publication:

Bryson, S; Julien, JP; Isenman, DE; Kunert, R; Katinger, H; Pai, EF.
(2008): Crystal structure of the complex between the F(ab)' fragment of the cross-neutralizing anti-HIV-1 antibody 2F5 and the F(ab) fragment of its anti-idiotypic antibody 3H6.
J Mol Biol. 2008; 382(4):910-919 FullText FullText_BOKU

Abstract:
The monoclonal antibody 2175 neutralizes a broad range of human immunodeficiency virus-1 isolates via a conserved epitope on the viral glycoprotein gp41. The conformation of the principal epitope is a type I beta-turn centered on gp41 residues (DKW666)-D-664; in addition, binding studies indicate that residues N- and C-terminal to this core as well as structurally more distant parts of gp41 also contribute to the interaction. Ab2/3H6 is an anti-idiotypic antibody that inhibits the interaction between 2F5 and gp41 and as such, Ab2/3H6 may, in principle, possess a paratope that mimics the gp41 epitope. To establish the potential of Ab2/3H6 to serve as a guide for the design of vaccine components against human immunodeficiency virus, we investigated the crystal structure of the heterodimeric complex of Ab2/3H6 F-ab and 2F5 F-ab'. Ab2/3H6 F-ab binds to 2F5 F-ab' via a helix-like protrusion formed by residues (RYSPSLNTRL67(H))-R-58(H) of the 2F5 F-ab' variable domain and proximal to but not overlapping with the gp41 (DKW666)-D-664 epitope-binding pocket. This defines Ab2/3H6 as an anti-idiotypic antibody of the Ab2 gamma class, i.e., an antigen-inhibitable idiotype that does not carry the internal image of the linear primary gp41 (662)ELDKWAS(668) epitope. (C) 2008 Elsevier Ltd. All rights reserved.
Authors BOKU Wien:
Katinger Hermann
Kunert Renate
Find related publications in this database (using NML MeSH Indexing)
Amino Acid Sequence -
Animals -
Antibodies, Anti-Idiotypic - chemistry
Antibodies, Monoclonal - chemistry
Binding Sites -
Crystallography, X-Ray -
Epitopes - chemistry
HIV Antibodies - chemistry
HIV Envelope Protein gp41 - chemistry
HIV-1 - immunology
Humans -
Immunoglobulin Fab Fragments - chemistry
Mice -
Models, Molecular -
Molecular Sequence Data -
Neutralization Tests -

Find related publications in this database (Keywords)
HIV-1
gp41
antibody
anti-idiotypic
crystal structure


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