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Molecular Basis for the Binding Promiscuity of an Anti-p24 (HIV-1) Monoclonal Antibody

Identifieur interne : 003E01 ( Main/Merge ); précédent : 003E00; suivant : 003E02

Molecular Basis for the Binding Promiscuity of an Anti-p24 (HIV-1) Monoclonal Antibody

Auteurs : Achim Kramer [Allemagne] ; Thomas Keitel [Allemagne] ; Karsten Winkler [Allemagne] ; Walter Stöcklein [Allemagne] ; Wolfgang Höhne [Allemagne] ; Jens Schneider-Mergener [Allemagne]

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RBID : ISTEX:C9559E952EA1497BFD096411604E6BD1BE470EFF

English descriptors

Abstract

Abstract: Multiple binding capabilities utilized by specific protein-to-protein interactions in molecular recognition events are being documented increasingly but remain poorly understood at the molecular level. We identified five unrelated peptides that compete with each other for binding to the paratope region of the monoclonal anti-p24 (HIV-1) antibody CB4-1 by using a synthetic positional scanning combinatorial library XXXX[B1,B2, B3,X1,X2,X3]XXXX (14 mers; 68,590 peptide mixtures in total) prepared by spot synthesis. Complete sets of substitution analogs of the five peptides revealed key interacting residues, information that led to the construction of binding supertopes derived from each peptide. These supertope sequences were identified in hundreds of heterologous proteins, and those proteins that could be obtained were shown to bind CB4-1. Implications of these findings for immune escape mechanisms and autoimmunity are discussed.

Url:
DOI: 10.1016/S0092-8674(00)80468-7

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ISTEX:C9559E952EA1497BFD096411604E6BD1BE470EFF

Le document en format XML

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<term>Amino acids</term>
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<div type="abstract" xml:lang="en">Abstract: Multiple binding capabilities utilized by specific protein-to-protein interactions in molecular recognition events are being documented increasingly but remain poorly understood at the molecular level. We identified five unrelated peptides that compete with each other for binding to the paratope region of the monoclonal anti-p24 (HIV-1) antibody CB4-1 by using a synthetic positional scanning combinatorial library XXXX[B1,B2, B3,X1,X2,X3]XXXX (14 mers; 68,590 peptide mixtures in total) prepared by spot synthesis. Complete sets of substitution analogs of the five peptides revealed key interacting residues, information that led to the construction of binding supertopes derived from each peptide. These supertope sequences were identified in hundreds of heterologous proteins, and those proteins that could be obtained were shown to bind CB4-1. Implications of these findings for immune escape mechanisms and autoimmunity are discussed.</div>
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