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

Identifieur interne : 003D46 ( Main/Exploration ); précédent : 003D45; suivant : 003D47

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]

Source :

RBID : ISTEX:C9559E952EA1497BFD096411604E6BD1BE470EFF

Descripteurs français

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


Affiliations:


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Le document en format XML

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<term>Animals</term>
<term>Antibodies, Monoclonal</term>
<term>Antibody Specificity</term>
<term>Binding Sites, Antibody</term>
<term>Energy Transfer</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>HIV Antibodies</term>
<term>HIV Core Protein p24 (chemistry)</term>
<term>HIV Core Protein p24 (immunology)</term>
<term>HIV-1 (immunology)</term>
<term>Humans</term>
<term>Immunoglobulin Fab Fragments</term>
<term>Microscopy, Fluorescence</term>
<term>Models, Molecular</term>
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<term>Oligopeptides (chemistry)</term>
<term>Peptide Library</term>
<term>Protein Conformation</term>
<term>Sequence Alignment</term>
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<term>Alignement de séquences</term>
<term>Animaux</term>
<term>Anticorps anti-VIH</term>
<term>Anticorps monoclonaux</term>
<term>Banque de peptides</term>
<term>Conformation des protéines</term>
<term>Données de séquences moléculaires</term>
<term>Fragments Fab d'immunoglobuline</term>
<term>Humains</term>
<term>Microscopie de fluorescence</term>
<term>Modèles moléculaires</term>
<term>Oligopeptides ()</term>
<term>Protéine de capside p24 du VIH ()</term>
<term>Protéine de capside p24 du VIH (immunologie)</term>
<term>Sites de fixation des anticorps</term>
<term>Spécificité des anticorps</term>
<term>Séquence d'acides aminés</term>
<term>Test ELISA</term>
<term>Transfert d'énergie</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie)</term>
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<term>Oligopeptides</term>
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<term>Protéine de capside p24 du VIH</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
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<term>HIV-1</term>
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<term>Adjacent positions</term>
<term>Affinity</term>
<term>Alanine residues</term>
<term>Alcohol dehydrogenase</term>
<term>Amino</term>
<term>Amino Acid Sequence</term>
<term>Amino acids</term>
<term>Animals</term>
<term>Antibodies, Monoclonal</term>
<term>Antibody</term>
<term>Antibody Specificity</term>
<term>Antibody binding</term>
<term>Antibody binding studies</term>
<term>Antibody polyspecificity</term>
<term>Association rate</term>
<term>Autoimmune diseases</term>
<term>Biacore measurements</term>
<term>Binding</term>
<term>Binding Sites, Antibody</term>
<term>Binding affinities</term>
<term>Binding experiments</term>
<term>Binding modes</term>
<term>Binding peptides</term>
<term>Binding promiscuity</term>
<term>Binding studies</term>
<term>Biotinylated peptides</term>
<term>Bovine serum albumin</term>
<term>Candidapepsin</term>
<term>Cellulose membranes</term>
<term>Coli</term>
<term>Combinatorial</term>
<term>Combinatorial libraries</term>
<term>Combinatorial peptide libraries</term>
<term>Competitive elisa</term>
<term>Complete regeneration</term>
<term>Complete sets</term>
<term>Continuous cellulose membranes</term>
<term>Corresponding proteins</term>
<term>Database</term>
<term>Database search</term>
<term>Database searches</term>
<term>Different binding modes</term>
<term>Different binding motifs</term>
<term>Different peptides</term>
<term>Dissociation constants</term>
<term>Elisa</term>
<term>Energy Transfer</term>
<term>Energy transfer</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Epitope</term>
<term>Evaluation software</term>
<term>First screening step</term>
<term>Foreign pathogens</term>
<term>Generous gift</term>
<term>HIV Antibodies</term>
<term>Heavy chain</term>
<term>Heterologous</term>
<term>Heterologous proteins</term>
<term>Humans</term>
<term>Hydrophobic contacts</term>
<term>Immunoglobulin Fab Fragments</term>
<term>Immunol</term>
<term>Inhibition constants</term>
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<term>Kramer</term>
<term>Light chain</term>
<term>Microscopy, Fluorescence</term>
<term>Microtiter plates</term>
<term>Models, Molecular</term>
<term>Molecular Sequence Data</term>
<term>Molecular basis</term>
<term>Molecular mimicry</term>
<term>Monoclonal</term>
<term>Monoclonal antibody</term>
<term>Mutant</term>
<term>Mutation</term>
<term>Natural antigen</term>
<term>Overall view</term>
<term>Peptide</term>
<term>Peptide Library</term>
<term>Peptide epitope</term>
<term>Peptide gatpedlnqklagn</term>
<term>Peptide libraries</term>
<term>Peptide mixtures</term>
<term>Peptide sequences</term>
<term>Pinilla</term>
<term>Polymerase chain reaction</term>
<term>Polyspecificity</term>
<term>Positional scanning</term>
<term>Promiscuity</term>
<term>Protein Conformation</term>
<term>Protein regions</term>
<term>Protein samples</term>
<term>Rapid identification</term>
<term>Relevant peptide</term>
<term>Room temperature</term>
<term>Same region</term>
<term>Scfv</term>
<term>Scfv fragments</term>
<term>Sequence Alignment</term>
<term>Single chain</term>
<term>Single substitution analogs</term>
<term>Small letters</term>
<term>Sodium carbonate buffer</term>
<term>Software pcgene</term>
<term>Soluble proteins</term>
<term>Spot synthesis</term>
<term>Strongest binding peptides</term>
<term>Structural basis</term>
<term>Structural requirements</term>
<term>Substantial loss</term>
<term>Substantial number</term>
<term>Substitution</term>
<term>Substitution analogs</term>
<term>Substitutional</term>
<term>Substitutional analyses</term>
<term>Substitutional analysis</term>
<term>Supertope</term>
<term>Supertope analysis</term>
<term>Supertope delineation</term>
<term>Supertope peptides</term>
<term>Supertopes</term>
<term>Total volume</term>
<term>Tryptophan residues</term>
<term>Umud</term>
<term>Umud protein</term>
<term>Unpublished data</term>
<term>Unrelated peptides</term>
<term>Variable regions</term>
<term>Various concentrations</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Alignement de séquences</term>
<term>Animaux</term>
<term>Anticorps anti-VIH</term>
<term>Anticorps monoclonaux</term>
<term>Banque de peptides</term>
<term>Conformation des protéines</term>
<term>Données de séquences moléculaires</term>
<term>Fragments Fab d'immunoglobuline</term>
<term>Humains</term>
<term>Microscopie de fluorescence</term>
<term>Modèles moléculaires</term>
<term>Oligopeptides</term>
<term>Protéine de capside p24 du VIH</term>
<term>Sites de fixation des anticorps</term>
<term>Spécificité des anticorps</term>
<term>Séquence d'acides aminés</term>
<term>Test ELISA</term>
<term>Transfert d'énergie</term>
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<front>
<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>
</front>
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<name sortKey="Kramer, Achim" sort="Kramer, Achim" uniqKey="Kramer A" first="Achim" last="Kramer">Achim Kramer</name>
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<name sortKey="Hohne, Wolfgang" sort="Hohne, Wolfgang" uniqKey="Hohne W" first="Wolfgang" last="Höhne">Wolfgang Höhne</name>
<name sortKey="Keitel, Thomas" sort="Keitel, Thomas" uniqKey="Keitel T" first="Thomas" last="Keitel">Thomas Keitel</name>
<name sortKey="Schneider Mergener, Jens" sort="Schneider Mergener, Jens" uniqKey="Schneider Mergener J" first="Jens" last="Schneider-Mergener">Jens Schneider-Mergener</name>
<name sortKey="Stocklein, Walter" sort="Stocklein, Walter" uniqKey="Stocklein W" first="Walter" last="Stöcklein">Walter Stöcklein</name>
<name sortKey="Winkler, Karsten" sort="Winkler, Karsten" uniqKey="Winkler K" first="Karsten" last="Winkler">Karsten Winkler</name>
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