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Cryo-EM structure of Alzheimer’s disease tau filaments with PET ligand MK-6240
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...
| Autores principales: | , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Cold Spring Harbor Laboratory
2023
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542181/ https://www.ncbi.nlm.nih.gov/pubmed/37790438 http://dx.doi.org/10.1101/2023.09.22.558671 |
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| author | Kunach, Peter Vaquer-Alicea, Jaime Smith, Matthew S. Hopewell, Robert Monistrol, Jim Moquin, Luc Therriault, Joseph Tissot, Cecile Rahmouni, Nesrine Massarweh, Gassan Soucy, Jean-Paul Guiot, Marie-Christine Shoichet, Brian K. Rosa-Neto, Pedro Diamond, Marc I. Shahmoradian, Sarah H. |
| author_facet | Kunach, Peter Vaquer-Alicea, Jaime Smith, Matthew S. Hopewell, Robert Monistrol, Jim Moquin, Luc Therriault, Joseph Tissot, Cecile Rahmouni, Nesrine Massarweh, Gassan Soucy, Jean-Paul Guiot, Marie-Christine Shoichet, Brian K. Rosa-Neto, Pedro Diamond, Marc I. Shahmoradian, Sarah H. |
| author_sort | Kunach, Peter |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-10542181 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | Cold Spring Harbor Laboratory |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-105421812023-10-03 Cryo-EM structure of Alzheimer’s disease tau filaments with PET ligand MK-6240 Kunach, Peter Vaquer-Alicea, Jaime Smith, Matthew S. Hopewell, Robert Monistrol, Jim Moquin, Luc Therriault, Joseph Tissot, Cecile Rahmouni, Nesrine Massarweh, Gassan Soucy, Jean-Paul Guiot, Marie-Christine Shoichet, Brian K. Rosa-Neto, Pedro Diamond, Marc I. Shahmoradian, Sarah H. bioRxiv Article 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. Cold Spring Harbor Laboratory 2023-09-22 /pmc/articles/PMC10542181/ /pubmed/37790438 http://dx.doi.org/10.1101/2023.09.22.558671 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator. |
| spellingShingle | Article Kunach, Peter Vaquer-Alicea, Jaime Smith, Matthew S. Hopewell, Robert Monistrol, Jim Moquin, Luc Therriault, Joseph Tissot, Cecile Rahmouni, Nesrine Massarweh, Gassan Soucy, Jean-Paul Guiot, Marie-Christine Shoichet, Brian K. Rosa-Neto, Pedro Diamond, Marc I. Shahmoradian, Sarah H. Cryo-EM structure of Alzheimer’s disease tau filaments with PET ligand MK-6240 |
| title | Cryo-EM structure of Alzheimer’s disease tau filaments with PET ligand MK-6240 |
| title_full | Cryo-EM structure of Alzheimer’s disease tau filaments with PET ligand MK-6240 |
| title_fullStr | Cryo-EM structure of Alzheimer’s disease tau filaments with PET ligand MK-6240 |
| title_full_unstemmed | Cryo-EM structure of Alzheimer’s disease tau filaments with PET ligand MK-6240 |
| title_short | Cryo-EM structure of Alzheimer’s disease tau filaments with PET ligand MK-6240 |
| title_sort | cryo-em structure of alzheimer’s disease tau filaments with pet ligand mk-6240 |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542181/ https://www.ncbi.nlm.nih.gov/pubmed/37790438 http://dx.doi.org/10.1101/2023.09.22.558671 |
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