5e2t: Difference between revisions

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~~'''Unreleased structure'''~~

The ~~entry 5e2t~~ is ~~ON HOLD~~

==Crystal structure of anti-TAU antibody AT8 FAB==

== Structural highlights ==

<table><tr><td colspan='2'>[[5e2t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E2T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E2T FirstGlance]. <br>

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5e2t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e2t OCA], [https://pdbe.org/5e2t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e2t RCSB], [https://www.ebi.ac.uk/pdbsum/5e2t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e2t ProSAT]</span></td></tr>

</table>

== 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.

~~Authors:~~ Malia, T., ~~Teplyakov~~, A.

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>

~~Description~~: ~~CRYSTAL STRUCTURE OF ANTI-TAU ANTIBODY AT8 FAB~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

[[Category: Malia, T]]

[[Category: Teplyakov, A]]

== References ==

__TOC__

</StructureSection>

[[Category: Large Structures]]

[[Category: Mus musculus]]

[[Category: Malia T]]

[[Category: Teplyakov A]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5e2t is ON HOLD
+==Crystal structure of anti-TAU antibody AT8 FAB==
+<StructureSection load='5e2t' size='340' side='right'caption='[[5e2t]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5e2t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E2T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E2T FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5e2t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e2t OCA], [https://pdbe.org/5e2t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e2t RCSB], [https://www.ebi.ac.uk/pdbsum/5e2t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e2t ProSAT]</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.
-Authors: Malia, T., Teplyakov, A.
+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>
-Description: CRYSTAL STRUCTURE OF ANTI-TAU ANTIBODY AT8 FAB
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Malia, T]]
+<div class="pdbe-citations 5e2t" style="background-color:#fffaf0;"></div>
-[[Category: Teplyakov, A]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Malia T]]
+[[Category: Teplyakov A]]