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TitleCryo-EM structure of Alzheimer's disease tau filaments with PET ligand MK-6240.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 8497, Year 2024
Publish dateOct 1, 2024
AuthorsPeter 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 AbstractPositron 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.
External linksNat Commun / PubMed:39353896 / PubMed Central
MethodsEM (helical sym.)
Resolution2.31 Å
Structure data

42463

8uq7

EMDB-42463, PDB-8uq7:
Alzheimer's disease PHF complexed with PET ligand MK-6240
Method: EM (helical sym.) / Resolution: 2.31 Å

Chemicals


ChemComp, No image

ChemComp-X6R:
Unknown entry

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / MK-6240 PET Ligand / AD PHF

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