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-Structure paper
タイトル | Cryo-EM structure of Alzheimer's disease tau filaments with PET ligand MK-6240. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 8497, Year 2024 |
掲載日 | 2024年10月1日 |
![]() | Peter Kunach / Jaime Vaquer-Alicea / Matthew S Smith / Jim Monistrol / Robert Hopewell / Luc Moquin / Joseph Therriault / Cecile Tissot / Nesrine Rahmouni / Gassan Massarweh / Jean-Paul Soucy / Marie-Christine Guiot / Brian K Shoichet / Pedro Rosa-Neto / Marc I Diamond / Sarah H Shahmoradian / ![]() |
PubMed 要旨 | Positron Emission Tomography (PET) ligands have advanced Alzheimer's disease (AD) diagnosis and treatment. Using autoradiography and cryo-EM, we identify AD brain tissue with elevated tau burden, ...Positron Emission Tomography (PET) ligands have advanced Alzheimer's disease (AD) diagnosis and treatment. Using autoradiography and cryo-EM, we identify AD brain tissue with elevated tau burden, purify filaments, and determine 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 353, 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. |
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手法 | EM (らせん対称) |
解像度 | 2.31 Å |
構造データ | EMDB-42463, PDB-8uq7: |
化合物 | ![]()
ChemComp-X6R: |
由来 |
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![]() | PROTEIN FIBRIL / MK-6240 PET Ligand / AD PHF |