A Phosphorylation-Induced Turn Defines the Alzheimer's Disease AT8 Antibody Epitope on the Tau Protein.
Identifieur interne : 003030 ( PubMed/Checkpoint ); précédent : 003029; suivant : 003031A Phosphorylation-Induced Turn Defines the Alzheimer's Disease AT8 Antibody Epitope on the Tau Protein.
Auteurs : Neha S. Gandhi ; Isabelle Landrieu ; Cillian Byrne [France] ; Predrag Kukic ; Laziza Amniai ; François-Xavier Cantrelle ; Jean-Michel Wieruszeski ; Ricardo L. Mancera ; Yves Jacquot [France] ; Guy Lippens [France]Source :
- Angewandte Chemie (International ed. in English) [ 1521-3773 ] ; 2015.
Descripteurs français
- KwdFr :
- Anticorps monoclonaux (immunologie), Cartographie épitopique, Humains, Maladie d'Alzheimer (immunologie), Maladie d'Alzheimer (métabolisme), Phosphorylation, Protéines tau (), Protéines tau (immunologie), Protéines tau (métabolisme), Résonance magnétique nucléaire biomoléculaire, Simulation de dynamique moléculaire, Épitopes (), Épitopes (immunologie).
- MESH :
English descriptors
- KwdEn :
- Alzheimer Disease (immunology), Alzheimer Disease (metabolism), Antibodies, Monoclonal (immunology), Epitope Mapping, Epitopes (chemistry), Epitopes (immunology), Humans, Molecular Dynamics Simulation, Nuclear Magnetic Resonance, Biomolecular, Phosphorylation, tau Proteins (chemistry), tau Proteins (immunology), tau Proteins (metabolism).
- MESH :
- chemical , chemistry : Epitopes, tau Proteins.
- chemical , immunology : Antibodies, Monoclonal, Epitopes, tau Proteins.
- immunology : Alzheimer Disease.
- metabolism : Alzheimer Disease, tau Proteins.
- Epitope Mapping, Humans, Molecular Dynamics Simulation, Nuclear Magnetic Resonance, Biomolecular, Phosphorylation.
Abstract
Post mortem biochemical staging of Alzheimer's disease is currently based on immunochemical analysis of brain slices with the AT8 antibody. The epitope of AT8 is described around the pSer202/pThr205 region of the hyperphosphorylated form of the neuronal protein tau. In this study, NMR spectroscopy was used to precisely map the AT8 epitope on phosphorylated tau, and derive its defining structural features by a combination of NMR analyses and molecular dynamics. A particular turn conformation is stabilized by a hydrogen bond of the phosphorylated Thr205 residue to the amide proton of Gly207, and is further stabilized by the two Arg residues opposing the pSer202/pThr205.
DOI: 10.1002/anie.201501898
PubMed: 25881502
Affiliations:
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pubmed:25881502Le document en format XML
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<front><div type="abstract" xml:lang="en">Post mortem biochemical staging of Alzheimer's disease is currently based on immunochemical analysis of brain slices with the AT8 antibody. The epitope of AT8 is described around the pSer202/pThr205 region of the hyperphosphorylated form of the neuronal protein tau. In this study, NMR spectroscopy was used to precisely map the AT8 epitope on phosphorylated tau, and derive its defining structural features by a combination of NMR analyses and molecular dynamics. A particular turn conformation is stabilized by a hydrogen bond of the phosphorylated Thr205 residue to the amide proton of Gly207, and is further stabilized by the two Arg residues opposing the pSer202/pThr205.</div>
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<Abstract><AbstractText>Post mortem biochemical staging of Alzheimer's disease is currently based on immunochemical analysis of brain slices with the AT8 antibody. The epitope of AT8 is described around the pSer202/pThr205 region of the hyperphosphorylated form of the neuronal protein tau. In this study, NMR spectroscopy was used to precisely map the AT8 epitope on phosphorylated tau, and derive its defining structural features by a combination of NMR analyses and molecular dynamics. A particular turn conformation is stabilized by a hydrogen bond of the phosphorylated Thr205 residue to the amide proton of Gly207, and is further stabilized by the two Arg residues opposing the pSer202/pThr205.</AbstractText>
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<name sortKey="Cantrelle, Francois Xavier" sort="Cantrelle, Francois Xavier" uniqKey="Cantrelle F" first="François-Xavier" last="Cantrelle">François-Xavier Cantrelle</name>
<name sortKey="Gandhi, Neha S" sort="Gandhi, Neha S" uniqKey="Gandhi N" first="Neha S" last="Gandhi">Neha S. Gandhi</name>
<name sortKey="Kukic, Predrag" sort="Kukic, Predrag" uniqKey="Kukic P" first="Predrag" last="Kukic">Predrag Kukic</name>
<name sortKey="Landrieu, Isabelle" sort="Landrieu, Isabelle" uniqKey="Landrieu I" first="Isabelle" last="Landrieu">Isabelle Landrieu</name>
<name sortKey="Mancera, Ricardo L" sort="Mancera, Ricardo L" uniqKey="Mancera R" first="Ricardo L" last="Mancera">Ricardo L. Mancera</name>
<name sortKey="Wieruszeski, Jean Michel" sort="Wieruszeski, Jean Michel" uniqKey="Wieruszeski J" first="Jean-Michel" last="Wieruszeski">Jean-Michel Wieruszeski</name>
</noCountry>
<country name="France"><region name="Île-de-France"><name sortKey="Byrne, Cillian" sort="Byrne, Cillian" uniqKey="Byrne C" first="Cillian" last="Byrne">Cillian Byrne</name>
</region>
<name sortKey="Jacquot, Yves" sort="Jacquot, Yves" uniqKey="Jacquot Y" first="Yves" last="Jacquot">Yves Jacquot</name>
<name sortKey="Lippens, Guy" sort="Lippens, Guy" uniqKey="Lippens G" first="Guy" last="Lippens">Guy Lippens</name>
</country>
</tree>
</affiliations>
</record>
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