5e2v: Difference between revisions
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==Anti-TAU AT8 FAB with doubly phosphorylated TAU peptide== | |||
<StructureSection load='5e2v' size='340' side='right' caption='[[5e2v]], [[Resolution|resolution]] 1.64Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5e2v]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E2V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E2V FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5e2w|5e2w]], [[5e2u|5e2u]], [[5e2t|5e2t]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5e2v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e2v OCA], [http://pdbe.org/5e2v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e2v RCSB], [http://www.ebi.ac.uk/pdbsum/5e2v PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Microtubule-associated protein tau becomes abnormally phosphorylated in Alzheimer's disease and other tauopathies and forms aggregates of paired helical filaments (PHF-tau). AT8 is a PHF-tau specific monoclonal antibody that is a commonly used marker of neuropathology because of its recognition of abnormally phosphorylated tau. Previous reports described the AT8 epitope to include pS202/pT205. Our studies support and extend previous findings by also identifying pS208 as part of the binding epitope. We characterized the phosphoepitope of AT8 through both peptide binding studies and co-structures with phosphopeptides. From the co-crystal structure of AT8 Fab with the di-phosphorylated (pS202/pT205) peptide it appeared that an additional phosphorylation at S208 would also be accommodated by AT8. Phosphopeptide binding studies showed that AT8 bound to the triply phosphorylated tau peptide (pS202/pT205/pS208) 30-fold stronger than to the pS202/pT205 peptide, supporting the role of pS208 in AT8 recognition. We also show that the binding kinetics of the triply phosphorylated peptide pS202/pT205/pS208 was remarkably similar to that of PHF-tau. The co-structure of AT8 Fab with a pS202/pT205/pS208 peptide shows that the interaction interface involves all six CDRs and tau residues 202-209. All three phosphorylation sites are recognized by AT8, with pT205 acting as the anchor. Crystallization of the Fab/peptide complex under acidic conditions shows that CDR-L2 is prone to unfolding and precludes peptide binding, and may suggest a general instability in the antibody. This article is protected by copyright. All rights reserved. | |||
Epitope mapping and structural basis for the recognition of phosphorylated tau by the anti-tau antibody AT8.,Malia TJ, Teplyakov A, Ernst R, Wu SJ, Lacy ER, Liu X, Vandermeeren M, Mercken M, Luo J, Sweet RW, Gilliland GL Proteins. 2016 Jan 21. doi: 10.1002/prot.24988. PMID:26800003<ref>PMID:26800003</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5e2v" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Malia, T]] | [[Category: Malia, T]] | ||
[[Category: Teplyakov, A]] | [[Category: Teplyakov, A]] | ||
[[Category: Immune system]] | |||