%0 Preprint
%T Cryo-EM structure of Alzheimer's disease tau filaments with PET ligand MK-6240.
%A Kunach P
%A Vaquer-Alicea J
%A Smith MS
%A Hopewell R
%A Monistrol J
%A Moquin L
%A Therriault J
%A Tissot C
%A Rahmouni N
%A Massarweh G
%A Soucy JP
%A Guiot MC
%A Shoichet BK
%A Rosa-Neto P
%A Diamond MI
%A Shahmoradian SH
%J bioRxiv
%V 0
%N 0
%D 2023 Sep 22
%M 37790438
暂无%R 10.1101/2023.09.22.558671
%X Positron Emission Tomography (PET) ligands have advanced Alzheimer's disease (AD) diagnosis and treatment. Using autoradiography and cryo-EM, we identified AD brain tissue with elevated tau burden, purified filaments, and determined the structure of second-generation high avidity PET ligand MK-6240 at 2.31 Å resolution, which bound at a 1:1 ratio within the cleft of tau paired-helical filament (PHF), engaging with glutamine 351, lysine K353, and isoleucine 360. This information elucidates the basis of MK-6240 PET in quantifying PHF deposits in AD and may facilitate the structure-based design of superior ligands against tau amyloids.