6DCV

Crystal structure of human anti-tau antibody CBTAU-27.1

6DCV の概要

• エントリーDOI: 10.2210/pdb6dcv/pdb
• 分子名称: Light chain of CBTAU27.1 Fab, heavy chain of CBTAU-27.1 Fab, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: tau, fab, naturally occurring human antibody, common motif, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 99085.97

構造登録者

Zhu, X.,Zhang, H.,Wilson, I.A. (登録日: 2018-05-08, 公開日: 2018-06-06, 最終更新日: 2024-10-16)

主引用文献

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, M.H.,Zuijdgeest, D.,Borgers, M.,Dockx, K.,Stoop, E.J.M.,Yu, W.,Brinkman-van der Linden, E.C.,Ummenthum, K.,van Kolen, K.,Mercken, M.,Steinbacher, S.,de Marco, D.,Hoozemans, J.J.,Wilson, I.A.,Koudstaal, W.,Goudsmit, J.
A common antigenic motif recognized by naturally occurring human VH5-51/VL4-1 anti-tau antibodies with distinct functionalities.
Acta Neuropathol Commun, 6:43-43, 2018

PubMed Abstract: 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 V5-51/V4-1 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 V5-51 and V4-1 recognizes a common Pro-X-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.

PubMed: 29855358
DOI: 10.1186/s40478-018-0543-z

実験手法

X-RAY DIFFRACTION (1.9 Å)