3tpk: Difference between revisions
New page: '''Unreleased structure''' The entry 3tpk is ON HOLD Authors: Parthier, C, Morgado, I., Stubbs, M.T., Fandrich, M. Description: Crystal structure of the oligomer-specific KW1 antibody ... |
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==Crystal structure of the oligomer-specific KW1 antibody fragment== | |||
<StructureSection load='3tpk' size='340' side='right'caption='[[3tpk]], [[Resolution|resolution]] 1.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3tpk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelidae Camelidae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TPK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TPK 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]] 1.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=3tpk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tpk OCA], [https://pdbe.org/3tpk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tpk RCSB], [https://www.ebi.ac.uk/pdbsum/3tpk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tpk ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Oligomers are intermediates of the beta-amyloid (Abeta) peptide fibrillogenic pathway and are putative pathogenic culprits in Alzheimer's disease (AD). Here we report the biotechnological generation and biochemical characterization of an oligomer-specific antibody fragment, KW1. KW1 not only discriminates between oligomers and other Abeta conformations, such as fibrils or disaggregated peptide; it also differentiates between different types of Abeta oligomers, such as those formed by Abeta (1-40) and Abeta (1-42) peptide. This high selectivity of binding contrasts sharply with many other conformational antibodies that interact with a large number of structurally analogous but sequentially different antigens. X-ray crystallography, NMR spectroscopy, and peptide array measurements imply that KW1 recognizes oligomers through a hydrophobic and significantly aromatic surface motif that includes Abeta residues 18-20. KW1-positive oligomers occur in human AD brain samples and induce synaptic dysfunctions in living brain tissues. Bivalent KW1 potently neutralizes this effect and interferes with Abeta assembly. By altering a specific step of the fibrillogenic cascade, it prevents the formation of mature Abeta fibrils and induces the accumulation of nonfibrillar aggregates. Our data illuminate significant mechanistic differences in oligomeric and fibril recognition and suggest the considerable potential of KW1 in future studies to detect or inhibit specific types of Abeta conformers. | |||
Molecular basis of beta-amyloid oligomer recognition with a conformational antibody fragment.,Morgado I, Wieligmann K, Bereza M, Ronicke R, Meinhardt K, Annamalai K, Baumann M, Wacker J, Hortschansky P, Malesevic M, Parthier C, Mawrin C, Schiene-Fischer C, Reymann KG, Stubbs MT, Balbach J, Gorlach M, Horn U, Fandrich M Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12503-8. Epub 2012 Jul 18. PMID:22814377<ref>PMID:22814377</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3tpk" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Camelidae]] | |||
[[Category: Large Structures]] | |||
[[Category: Fandrich M]] | |||
[[Category: Morgado I]] | |||
[[Category: Parthier C]] | |||
[[Category: Stubbs MT]] | |||