TY - JOUR
T1 - Structural Basis for Recognition of a Unique Epitope by a Human Anti-tau Antibody
AU - Zhang, Heng
AU - Zhu, Xueyong
AU - Pascual, Gabriel
AU - Wadia, Jehangir S.
AU - Keogh, Elissa
AU - Hoozemans, Jeroen J.
AU - Siregar, Berdien
AU - Inganäs, Hanna
AU - Stoop, Esther J. M.
AU - Goudsmit, Jaap
AU - Apetri, Adrian
AU - Koudstaal, Wouter
AU - Wilson, Ian A.
PY - 2018
Y1 - 2018
N2 - Aggregation of the hyperphosphorylated protein tau into neurofibrillary tangles and neuropil threads is a hallmark of Alzheimer disease (AD). Identification and characterization of the epitopes recognized by anti-tau antibodies might shed light on the molecular mechanisms of AD pathogenesis. Here we report on the biochemical and structural characterization of a tau-specific monoclonal antibody CBTAU-24.1, which was isolated from the human memory B cell repertoire. Immunohistochemical staining with CBTAU-24.1 specifically detects pathological tau structures in AD brain samples. The crystal structure of CBTAU-24.1 Fab with a phosphorylated tau peptide revealed recognition of a unique epitope (Ser235-Leu243) in the tau proline-rich domain. Interestingly, the antibody can bind tau regardless of phosphorylation state of its epitope region and also recognizes both monomeric and paired helical filament tau irrespective of phosphorylation status. This human anti-tau antibody and its unique epitope may aid in development of diagnostics and/or therapeutic AD strategies.
AB - Aggregation of the hyperphosphorylated protein tau into neurofibrillary tangles and neuropil threads is a hallmark of Alzheimer disease (AD). Identification and characterization of the epitopes recognized by anti-tau antibodies might shed light on the molecular mechanisms of AD pathogenesis. Here we report on the biochemical and structural characterization of a tau-specific monoclonal antibody CBTAU-24.1, which was isolated from the human memory B cell repertoire. Immunohistochemical staining with CBTAU-24.1 specifically detects pathological tau structures in AD brain samples. The crystal structure of CBTAU-24.1 Fab with a phosphorylated tau peptide revealed recognition of a unique epitope (Ser235-Leu243) in the tau proline-rich domain. Interestingly, the antibody can bind tau regardless of phosphorylation state of its epitope region and also recognizes both monomeric and paired helical filament tau irrespective of phosphorylation status. This human anti-tau antibody and its unique epitope may aid in development of diagnostics and/or therapeutic AD strategies.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85059315634&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30318466
U2 - https://doi.org/10.1016/j.str.2018.08.012
DO - https://doi.org/10.1016/j.str.2018.08.012
M3 - Article
C2 - 30318466
SN - 0969-2126
VL - 26
SP - 1626-1634.e4
JO - Structure (London, England
JF - Structure (London, England
IS - 12
ER -