Phosphorylated and nonphosphorylated epitopes of the La/SSB autoantigen: comparison of their antigenic and conformational characteristics.
Identifieur interne : 000086 ( Ncbi/Curation ); précédent : 000085; suivant : 000087Phosphorylated and nonphosphorylated epitopes of the La/SSB autoantigen: comparison of their antigenic and conformational characteristics.
Auteurs : Nicolas Coudevylle [France] ; Dimitrios Rokas ; Maria Sakarellos-Daitsiotis ; Dimitrios Krikorian ; Eugenia Panou-Pomonis ; Constantinos Sakarellos ; Guy Boussard ; Manh Thong CungSource :
- Biopolymers [ 0006-3525 ] ; 2006.
Descripteurs français
- KwdFr :
- Autoantigènes (), Autoantigènes (immunologie), Cellules HeLa, Conformation moléculaire, Humains, Liaison hydrogène, Lupus érythémateux disséminé (immunologie), Lupus érythémateux disséminé (sang), Masse moléculaire, Microscopie confocale, Modèles moléculaires, Peptides (génétique), Peptides (immunologie), Phosphorylation, Ribonucléoprotéines (), Ribonucléoprotéines (immunologie), Résonance magnétique nucléaire biomoléculaire, Simulation numérique, Spectrométrie de masse, Spectrométrie de masse ESI, Syndrome de Gougerot-Sjögren (immunologie), Syndrome de Gougerot-Sjögren (sang), Séquence d'acides aminés, Test ELISA, Épitopes (), Épitopes (génétique), Épitopes (immunologie).
- MESH :
- génétique : Peptides, Épitopes.
- immunologie : Autoantigènes, Lupus érythémateux disséminé, Peptides, Ribonucléoprotéines, Syndrome de Gougerot-Sjögren, Épitopes.
- sang : Lupus érythémateux disséminé, Syndrome de Gougerot-Sjögren.
- Autoantigènes, Cellules HeLa, Conformation moléculaire, Humains, Liaison hydrogène, Masse moléculaire, Microscopie confocale, Modèles moléculaires, Phosphorylation, Ribonucléoprotéines, Résonance magnétique nucléaire biomoléculaire, Simulation numérique, Spectrométrie de masse, Spectrométrie de masse ESI, Séquence d'acides aminés, Test ELISA, Épitopes.
English descriptors
- KwdEn :
- Amino Acid Sequence, Autoantigens (chemistry), Autoantigens (classification), Autoantigens (immunology), Computer Simulation, Enzyme-Linked Immunosorbent Assay, Epitopes (chemistry), Epitopes (genetics), Epitopes (immunology), HeLa Cells, Humans, Hydrogen Bonding, Lupus Erythematosus, Systemic (blood), Lupus Erythematosus, Systemic (immunology), Mass Spectrometry, Microscopy, Confocal, Models, Molecular, Molecular Conformation, Molecular Weight, Nuclear Magnetic Resonance, Biomolecular, Peptides (genetics), Peptides (immunology), Phosphorylation, Ribonucleoproteins (chemistry), Ribonucleoproteins (classification), Ribonucleoproteins (immunology), Sjogren's Syndrome (blood), Sjogren's Syndrome (immunology), Spectrometry, Mass, Electrospray Ionization.
- MESH :
- chemical , chemistry : Autoantigens, Epitopes, Ribonucleoproteins.
- chemical , classification : Autoantigens, Ribonucleoproteins.
- chemical , genetics : Epitopes, Peptides.
- chemical , immunology : Autoantigens, Epitopes, Peptides, Ribonucleoproteins.
- blood : Lupus Erythematosus, Systemic, Sjogren's Syndrome.
- immunology : Lupus Erythematosus, Systemic, Sjogren's Syndrome.
- Amino Acid Sequence, Computer Simulation, Enzyme-Linked Immunosorbent Assay, HeLa Cells, Humans, Hydrogen Bonding, Mass Spectrometry, Microscopy, Confocal, Models, Molecular, Molecular Conformation, Molecular Weight, Nuclear Magnetic Resonance, Biomolecular, Phosphorylation, Spectrometry, Mass, Electrospray Ionization.
Abstract
La/SSB phosphoprotein is the target antigen of autoantibodies in sera of patients with Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). Among other structural and function motifs, four phosphorylation sites are encompassed in the primary sequence of La/SSB. Two of them (Thr-362 and Ser-366) are located within GSGKGKVQFQGKKTKFASDD (346-368) and one (Thr-302) within VTWEVLEGEVEKEALKKI (301-318), which are main B-cell epitopes of La/SSB. With the aim to investigate how phosphorylation, one of the most common posttranslational protein modifications, affects the antigenic and conformational characteristics of the La/SSB epitopes, we synthesized and studied the phosphorylated epitopes La/SSB(346-368)-P, La/SSB(359-368)-P, and La/SSB(301-318)-P with respect to their nonphosphorylated counterparts. Anti-La/SSB positive sera from SS and SLE patients are better recognized by the phosphorylated epitopes compared to their nonphosphorylated counterparts. Conformational analysis by (1)H nuclear magnetic resonance spectroscopy and molecular dynamics showed that the phosphorylated epitopes adopt different structural characteristics from those of the corresponding nonphosphorylated epitopes. It is concluded that phosphorylation can create neoepitopes with altered functions, compared to the nonphosphorylated epitopes, which might be seen from the immune system as "foreign."
DOI: 10.1002/bip.20458
PubMed: 16453388
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pubmed:16453388Le document en format XML
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<term>Autoantigens (chemistry)</term>
<term>Autoantigens (classification)</term>
<term>Autoantigens (immunology)</term>
<term>Computer Simulation</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>Epitopes (chemistry)</term>
<term>Epitopes (genetics)</term>
<term>Epitopes (immunology)</term>
<term>HeLa Cells</term>
<term>Humans</term>
<term>Hydrogen Bonding</term>
<term>Lupus Erythematosus, Systemic (blood)</term>
<term>Lupus Erythematosus, Systemic (immunology)</term>
<term>Mass Spectrometry</term>
<term>Microscopy, Confocal</term>
<term>Models, Molecular</term>
<term>Molecular Conformation</term>
<term>Molecular Weight</term>
<term>Nuclear Magnetic Resonance, Biomolecular</term>
<term>Peptides (genetics)</term>
<term>Peptides (immunology)</term>
<term>Phosphorylation</term>
<term>Ribonucleoproteins (chemistry)</term>
<term>Ribonucleoproteins (classification)</term>
<term>Ribonucleoproteins (immunology)</term>
<term>Sjogren's Syndrome (blood)</term>
<term>Sjogren's Syndrome (immunology)</term>
<term>Spectrometry, Mass, Electrospray Ionization</term>
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<term>Autoantigènes (immunologie)</term>
<term>Cellules HeLa</term>
<term>Conformation moléculaire</term>
<term>Humains</term>
<term>Liaison hydrogène</term>
<term>Lupus érythémateux disséminé (immunologie)</term>
<term>Lupus érythémateux disséminé (sang)</term>
<term>Masse moléculaire</term>
<term>Microscopie confocale</term>
<term>Modèles moléculaires</term>
<term>Peptides (génétique)</term>
<term>Peptides (immunologie)</term>
<term>Phosphorylation</term>
<term>Ribonucléoprotéines ()</term>
<term>Ribonucléoprotéines (immunologie)</term>
<term>Résonance magnétique nucléaire biomoléculaire</term>
<term>Simulation numérique</term>
<term>Spectrométrie de masse</term>
<term>Spectrométrie de masse ESI</term>
<term>Syndrome de Gougerot-Sjögren (immunologie)</term>
<term>Syndrome de Gougerot-Sjögren (sang)</term>
<term>Séquence d'acides aminés</term>
<term>Test ELISA</term>
<term>Épitopes ()</term>
<term>Épitopes (génétique)</term>
<term>Épitopes (immunologie)</term>
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<term>Epitopes</term>
<term>Ribonucleoproteins</term>
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<term>Ribonucleoproteins</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Epitopes</term>
<term>Peptides</term>
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<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Autoantigens</term>
<term>Epitopes</term>
<term>Peptides</term>
<term>Ribonucleoproteins</term>
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<term>Sjogren's Syndrome</term>
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<term>Lupus érythémateux disséminé</term>
<term>Peptides</term>
<term>Ribonucléoprotéines</term>
<term>Syndrome de Gougerot-Sjögren</term>
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<term>Sjogren's Syndrome</term>
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<term>Syndrome de Gougerot-Sjögren</term>
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<term>Computer Simulation</term>
<term>Enzyme-Linked Immunosorbent Assay</term>
<term>HeLa Cells</term>
<term>Humans</term>
<term>Hydrogen Bonding</term>
<term>Mass Spectrometry</term>
<term>Microscopy, Confocal</term>
<term>Models, Molecular</term>
<term>Molecular Conformation</term>
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<term>Nuclear Magnetic Resonance, Biomolecular</term>
<term>Phosphorylation</term>
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<term>Cellules HeLa</term>
<term>Conformation moléculaire</term>
<term>Humains</term>
<term>Liaison hydrogène</term>
<term>Masse moléculaire</term>
<term>Microscopie confocale</term>
<term>Modèles moléculaires</term>
<term>Phosphorylation</term>
<term>Ribonucléoprotéines</term>
<term>Résonance magnétique nucléaire biomoléculaire</term>
<term>Simulation numérique</term>
<term>Spectrométrie de masse</term>
<term>Spectrométrie de masse ESI</term>
<term>Séquence d'acides aminés</term>
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<front><div type="abstract" xml:lang="en">La/SSB phosphoprotein is the target antigen of autoantibodies in sera of patients with Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). Among other structural and function motifs, four phosphorylation sites are encompassed in the primary sequence of La/SSB. Two of them (Thr-362 and Ser-366) are located within GSGKGKVQFQGKKTKFASDD (346-368) and one (Thr-302) within VTWEVLEGEVEKEALKKI (301-318), which are main B-cell epitopes of La/SSB. With the aim to investigate how phosphorylation, one of the most common posttranslational protein modifications, affects the antigenic and conformational characteristics of the La/SSB epitopes, we synthesized and studied the phosphorylated epitopes La/SSB(346-368)-P, La/SSB(359-368)-P, and La/SSB(301-318)-P with respect to their nonphosphorylated counterparts. Anti-La/SSB positive sera from SS and SLE patients are better recognized by the phosphorylated epitopes compared to their nonphosphorylated counterparts. Conformational analysis by (1)H nuclear magnetic resonance spectroscopy and molecular dynamics showed that the phosphorylated epitopes adopt different structural characteristics from those of the corresponding nonphosphorylated epitopes. It is concluded that phosphorylation can create neoepitopes with altered functions, compared to the nonphosphorylated epitopes, which might be seen from the immune system as "foreign."</div>
</front>
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