View source for 6dcv


==Crystal structure of human anti-tau antibody CBTAU-27.1==
<StructureSection load='6dcv' size='340' side='right'caption='[[6dcv]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6dcv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DCV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DCV 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]] 1.9&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6dcv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dcv OCA], [https://pdbe.org/6dcv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dcv RCSB], [https://www.ebi.ac.uk/pdbsum/6dcv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dcv ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN] Defects in IGKC are the cause of immunoglobulin kappa light chain deficiency (IGKCD) [MIM:[https://omim.org/entry/614102 614102]. IGKCD is a disease characterized by the complete absence of immunoglobulin kappa chains.<ref>PMID:3931219</ref> 
== Function ==
[https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Misfolding and aggregation of tau protein are closely associated with the onset and progression of Alzheimer's Disease (AD). By interrogating IgG(+) memory B cells from asymptomatic donors with tau peptides, we have identified two somatically mutated VH5-51/VL4-1 antibodies. One of these, CBTAU-27.1, binds to the aggregation motif in the R3 repeat domain and blocks the aggregation of tau into paired helical filaments (PHFs) by sequestering monomeric tau. The other, CBTAU-28.1, binds to the N-terminal insert region and inhibits the spreading of tau seeds and mediates the uptake of tau aggregates into microglia by binding PHFs. Crystal structures revealed that the combination of VH5-51 and VL4-1 recognizes a common Pro-Xn-Lys motif driven by germline-encoded hotspot interactions while the specificity and thereby functionality of the antibodies are defined by the CDR3 regions. Affinity improvement led to improvement in functionality, identifying their epitopes as new targets for therapy and prevention of AD.

A common antigenic motif recognized by naturally occurring human VH5-51/VL4-1 anti-tau antibodies with distinct functionalities.,Apetri A, Crespo R, Juraszek J, Pascual G, Janson R, Zhu X, Zhang H, Keogh E, Holland T, Wadia J, Verveen H, Siregar B, Mrosek M, Taggenbrock R, Ameijde J, Inganas H, van Winsen M, Koldijk MH, Zuijdgeest D, Borgers M, Dockx K, Stoop EJM, Yu W, Brinkman-van der Linden EC, Ummenthum K, van Kolen K, Mercken M, Steinbacher S, de Marco D, Hoozemans JJ, Wilson IA, Koudstaal W, Goudsmit J Acta Neuropathol Commun. 2018 May 31;6(1):43. doi: 10.1186/s40478-018-0543-z. PMID:29855358<ref>PMID:29855358</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6dcv" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wilson IA]]
[[Category: Zhang H]]
[[Category: Zhu X]]