M
Meredith E. Jackrel
Researcher at University of Pennsylvania
Publications - 37
Citations - 1853
Meredith E. Jackrel is an academic researcher from University of Pennsylvania. The author has contributed to research in topics: Proteotoxicity & Neurodegeneration. The author has an hindex of 19, co-authored 31 publications receiving 1476 citations. Previous affiliations of Meredith E. Jackrel include Washington University in St. Louis & Yale University.
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Journal ArticleDOI
Nuclear-Import Receptors Reverse Aberrant Phase Transitions of RNA-Binding Proteins with Prion-like Domains
Lin Guo,Hong Joo Kim,Hejia Wang,John Monaghan,Fernande Freyermuth,Julie C. Sung,Kevin J. O'Donovan,Charlotte M. Fare,Zamia Diaz,Nikita Singh,Zi Chao Zhang,Zi Chao Zhang,Maura Coughlin,Elizabeth A. Sweeny,Morgan E. DeSantis,Meredith E. Jackrel,Christopher B. Rodell,Jason A. Burdick,Oliver D. King,Aaron D. Gitler,Clotilde Lagier-Tourenne,Udai Bhan Pandey,Yuh Min Chook,J. Paul Taylor,J. Paul Taylor,James Shorter +25 more
TL;DR: Karyopherin-β2 prevents RBPs with PY-NLSs accumulating in stress granules, restores nuclear RBP localization and function, and rescues degeneration caused by disease-linked FUS and hnRNPA2, establishing that NIRs therapeutically restore RBP homeostasis and mitigate neurodegeneration.
Journal ArticleDOI
Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104.
Stephanie N. Gates,Adam L. Yokom,JiaBei Lin,Meredith E. Jackrel,Alexandrea N. Rizo,Nathan M. Kendsersky,Courtney E. Buell,Elizabeth A. Sweeny,Korrie L. Mack,Edward Chuang,Mariana P. Torrente,Mariana P. Torrente,Min Su,James Shorter,Daniel R. Southworth +14 more
TL;DR: Cryo-electron microscopy structures of the Hsp104 disaggregase bound to an unfolded polypeptide substrate in its channel reveal substrate interactions and two different translocation states and helps explain how this molecular machine can solubilize protein aggregates and amyloids.
Journal ArticleDOI
Potentiated Hsp104 Variants Antagonize Diverse Proteotoxic Misfolding Events
Meredith E. Jackrel,Morgan E. DeSantis,Bryan A. Martinez,Laura M. Castellano,Rachel M. Stewart,Kim A. Caldwell,Guy A. Caldwell,James Shorter +7 more
TL;DR: It is established that disease-associated aggregates and amyloid are tractable targets and that enhanced disaggregases can restore proteostasis and mitigate neurodegeneration.
Journal ArticleDOI
Operational Plasticity Enables Hsp104 to Disaggregate Diverse Amyloid and Nonamyloid Clients
Morgan E. DeSantis,Eunice H. Leung,Elizabeth A. Sweeny,Meredith E. Jackrel,Mimi Cushman-Nick,Alexandra Neuhaus-Follini,Shilpa Vashist,Matthew A. Sochor,M. Noelle Knight,James Shorter +9 more
TL;DR: Operational plasticity enables Hsp104 to robustly dissolve amyloid and nonamyloid clients, which impose distinct mechanical demands.
Journal ArticleDOI
Spiral architecture of the Hsp104 disaggregase reveals the basis for polypeptide translocation
Adam L. Yokom,Stephanie N. Gates,Meredith E. Jackrel,Korrie L. Mack,Min Su,James Shorter,Daniel R. Southworth +6 more
TL;DR: The cryo-EM structure of wild-type Saccharomyces cerevisiae Hsp104 in the ATP state is determined, revealing a near-helical hexamer architecture that coordinates the mechanical power of the 12 AAA+ domains for disaggregation and explaining roles in ATP hydrolysis and protein disaggregation.