ISDA: 8UQ7

Deposition Date 2023-10-23

Release Date 2024-09-04

Last Version Date 2024-10-23

Entry Detail

PDB ID:

8UQ7

Keywords:

PROTEIN FIBRIL

Title:

Alzheimer's disease PHF complexed with PET ligand MK-6240

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)

Method Details:

Experimental Method:

ELECTRON MICROSCOPY

Resolution:

2.31 Å

Aggregation State:

FILAMENT

Reconstruction Method:

HELICAL

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Microtubule-associated protei
Gene (Uniprot):MAPT
Chain IDs:A, B, C, D, E, F
Chain Length:75
Number of Molecules:6
Biological Source:Homo sapiens

UniProt ID:P10636 Pfam ID:PF00418

Ligand Molecules

X6R

Primary Citation

Cryo-EM structure of Alzheimer's disease tau filaments with PET ligand MK-6240.

Kunach, P, Vaquer-Alicea, J, Smith, M.S, Monistrol, J, Hopewell, R, Moquin, L, Therriault, J, Tissot, C, Rahmouni, N, Massarweh, G, Soucy, J.P, Guiot, M.C, Shoichet, B.K, Rosa-Neto, P, Diamond, M.I, Shahmoradian, S.H.Show

Nat Commun 15 8497 8497 (2024)

PMID: 39353896 DOI: 10.1038/s41467-024-52265-x

Abstact

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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Protein

Chemical

Disease

Primary Citation of related structures

Abstact

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