6dcw | pdb_00006dcw

Crystal structure of human anti-tau antibody CBTAU-27.1 Fab in complex with a human tau peptide

spinqualitylabelsall models 6dcw, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6dcw is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tau protein

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