Conformational epitopes recognized by protective anti-neisserial surface protein A antibodies.
Identifieur interne : 003226 ( Main/Curation ); précédent : 003225; suivant : 003227Conformational epitopes recognized by protective anti-neisserial surface protein A antibodies.
Auteurs : Victor C. Hou [États-Unis] ; Gregory R. Moe ; Zyde Raad ; Tomi Wuorimaa ; Dan M. GranoffSource :
- Infection and immunity [ 0019-9567 ] ; 2003.
Descripteurs français
- KwdFr :
- Animaux, Anticorps monoclonaux (immunologie), Conformation des protéines, Données de séquences moléculaires, Humains, Liposomes, Modèles moléculaires, Mutagenèse dirigée, Neisseria meningitidis (immunologie), Pliage des protéines, Protéines de la membrane externe bactérienne (), Protéines de la membrane externe bactérienne (génétique), Protéines de la membrane externe bactérienne (immunologie), Protéines recombinantes, Rats, Souris, Séquence d'acides aminés, Épitopes (immunologie).
- MESH :
- génétique : Protéines de la membrane externe bactérienne.
- immunologie : Anticorps monoclonaux, Neisseria meningitidis, Protéines de la membrane externe bactérienne, Épitopes.
- Animaux, Conformation des protéines, Données de séquences moléculaires, Humains, Liposomes, Modèles moléculaires, Mutagenèse dirigée, Pliage des protéines, Protéines de la membrane externe bactérienne, Protéines recombinantes, Rats, Souris, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antibodies, Monoclonal (immunology), Bacterial Outer Membrane Proteins (chemistry), Bacterial Outer Membrane Proteins (genetics), Bacterial Outer Membrane Proteins (immunology), Epitopes (immunology), Humans, Liposomes, Mice, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Neisseria meningitidis (immunology), Protein Conformation, Protein Folding, Rats, Recombinant Proteins.
- MESH :
- chemical , chemistry : Bacterial Outer Membrane Proteins.
- chemical , genetics : Bacterial Outer Membrane Proteins.
- chemical , immunology : Antibodies, Monoclonal, Bacterial Outer Membrane Proteins, Epitopes.
- immunology : Neisseria meningitidis.
- Amino Acid Sequence, Animals, Humans, Liposomes, Mice, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Protein Conformation, Protein Folding, Rats, Recombinant Proteins.
Abstract
NspA is a conserved membrane protein that elicits protective antibody responses in mice against Neisseria meningitidis. A recent crystallographic study showed that NspA adopts an eight-stranded beta-barrel structure when reconstituted in detergent. In order to define the segments of NspA-containing epitopes recognized by protective murine anti-NspA antibodies, we studied the binding of two bactericidal and protective anti-NspA monoclonal antibodies (MAbs), AL12 and 14C7. Neither MAb binds to overlapping synthetic peptides (10-mers, 12-mers, and cyclic 12-mers) corresponding to the entire mature sequence of NspA, or to denatured recombinant NspA (rNspA), although binding to the protein can be restored by refolding in liposomes. Based on the ability of the two MAbs to bind to Escherichia coli microvesicles prepared from a set of rNspA variants created by site-specific mutagenesis, the most important contacts between the MAbs and NspA appear to be located within the LGG segment of loop 3. The conformation of loop 2 also appears to be an important determinant, as particular combinations of residues in this segment resulted in loss of antibody binding. Thus, the two anti-NspA MAbs recognize discontinuous conformational epitopes that result from the close proximity of loops 2 and 3 in the three-dimensional structure of NspA. The data suggest that optimally immunogenic vaccines using rNspA will require formulations that permit proper folding of the protein.
DOI: 10.1128/iai.71.12.6844-6849.2003
PubMed: 14638771
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pubmed:14638771Le document en format XML
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Moe</name></author><author><name sortKey="Raad, Zyde" sort="Raad, Zyde" uniqKey="Raad Z" first="Zyde" last="Raad">Zyde Raad</name></author><author><name sortKey="Wuorimaa, Tomi" sort="Wuorimaa, Tomi" uniqKey="Wuorimaa T" first="Tomi" last="Wuorimaa">Tomi Wuorimaa</name></author><author><name sortKey="Granoff, Dan M" sort="Granoff, Dan M" uniqKey="Granoff D" first="Dan M" last="Granoff">Dan M. 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Hou</name><affiliation wicri:level="2"><nlm:affiliation>Children's Hospital Oakland Research Institute, Oakland, California, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Children's Hospital Oakland Research Institute, Oakland, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Moe, Gregory R" sort="Moe, Gregory R" uniqKey="Moe G" first="Gregory R" last="Moe">Gregory R. Moe</name></author><author><name sortKey="Raad, Zyde" sort="Raad, Zyde" uniqKey="Raad Z" first="Zyde" last="Raad">Zyde Raad</name></author><author><name sortKey="Wuorimaa, Tomi" sort="Wuorimaa, Tomi" uniqKey="Wuorimaa T" first="Tomi" last="Wuorimaa">Tomi Wuorimaa</name></author><author><name sortKey="Granoff, Dan M" sort="Granoff, Dan M" uniqKey="Granoff D" first="Dan M" last="Granoff">Dan M. Granoff</name></author></analytic><series><title level="j">Infection and immunity</title><idno type="ISSN">0019-9567</idno><imprint><date when="2003" type="published">2003</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Antibodies, Monoclonal (immunology)</term><term>Bacterial Outer Membrane Proteins (chemistry)</term><term>Bacterial Outer Membrane Proteins (genetics)</term><term>Bacterial Outer Membrane Proteins (immunology)</term><term>Epitopes (immunology)</term><term>Humans</term><term>Liposomes</term><term>Mice</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Mutagenesis, Site-Directed</term><term>Neisseria meningitidis (immunology)</term><term>Protein Conformation</term><term>Protein Folding</term><term>Rats</term><term>Recombinant Proteins</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps monoclonaux (immunologie)</term><term>Conformation des protéines</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Liposomes</term><term>Modèles moléculaires</term><term>Mutagenèse dirigée</term><term>Neisseria meningitidis (immunologie)</term><term>Pliage des protéines</term><term>Protéines de la membrane externe bactérienne ()</term><term>Protéines de la membrane externe bactérienne (génétique)</term><term>Protéines de la membrane externe bactérienne (immunologie)</term><term>Protéines recombinantes</term><term>Rats</term><term>Souris</term><term>Séquence d'acides aminés</term><term>Épitopes (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Bacterial Outer Membrane Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Bacterial Outer Membrane Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Bacterial Outer Membrane Proteins</term><term>Epitopes</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéines de la membrane externe bactérienne</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps monoclonaux</term><term>Neisseria meningitidis</term><term>Protéines de la membrane externe bactérienne</term><term>Épitopes</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Neisseria meningitidis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Humans</term><term>Liposomes</term><term>Mice</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Mutagenesis, Site-Directed</term><term>Protein Conformation</term><term>Protein Folding</term><term>Rats</term><term>Recombinant Proteins</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Conformation des protéines</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Liposomes</term><term>Modèles moléculaires</term><term>Mutagenèse dirigée</term><term>Pliage des protéines</term><term>Protéines de la membrane externe bactérienne</term><term>Protéines recombinantes</term><term>Rats</term><term>Souris</term><term>Séquence d'acides aminés</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">NspA is a conserved membrane protein that elicits protective antibody responses in mice against Neisseria meningitidis. A recent crystallographic study showed that NspA adopts an eight-stranded beta-barrel structure when reconstituted in detergent. In order to define the segments of NspA-containing epitopes recognized by protective murine anti-NspA antibodies, we studied the binding of two bactericidal and protective anti-NspA monoclonal antibodies (MAbs), AL12 and 14C7. Neither MAb binds to overlapping synthetic peptides (10-mers, 12-mers, and cyclic 12-mers) corresponding to the entire mature sequence of NspA, or to denatured recombinant NspA (rNspA), although binding to the protein can be restored by refolding in liposomes. Based on the ability of the two MAbs to bind to Escherichia coli microvesicles prepared from a set of rNspA variants created by site-specific mutagenesis, the most important contacts between the MAbs and NspA appear to be located within the LGG segment of loop 3. The conformation of loop 2 also appears to be an important determinant, as particular combinations of residues in this segment resulted in loss of antibody binding. Thus, the two anti-NspA MAbs recognize discontinuous conformational epitopes that result from the close proximity of loops 2 and 3 in the three-dimensional structure of NspA. The data suggest that optimally immunogenic vaccines using rNspA will require formulations that permit proper folding of the protein.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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