5e2v: Difference between revisions
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==Anti-TAU AT8 FAB with doubly phosphorylated TAU peptide== | ==Anti-TAU AT8 FAB with doubly phosphorylated TAU peptide== | ||
<StructureSection load='5e2v' size='340' side='right' caption='[[5e2v]], [[Resolution|resolution]] 1.64Å' scene=''> | <StructureSection load='5e2v' size='340' side='right'caption='[[5e2v]], [[Resolution|resolution]] 1.64Å' scene=''> | ||
== Structural highlights == | == 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:// | <table><tr><td colspan='2'>[[5e2v]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. 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://proteopedia.org/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> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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='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:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e2v ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 5e2v" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5e2v" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Tau protein|Tau protein]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Lk3 transgenic mice]] | |||
[[Category: Malia, T]] | [[Category: Malia, T]] | ||
[[Category: Teplyakov, A]] | [[Category: Teplyakov, A]] | ||
[[Category: Immune system]] | [[Category: Immune system]] | ||
Revision as of 09:41, 22 April 2020
Anti-TAU AT8 FAB with doubly phosphorylated TAU peptideAnti-TAU AT8 FAB with doubly phosphorylated TAU peptide
Structural highlights
Publication Abstract from PubMedMicrotubule-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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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