Daniel R. Southworth

This study reveals that Hsp104, an AAA+ ATPase, functions as a bidirectional, processive translocase by switching direction through biased stochastic conformational transitions.

The paper investigates how phosphorylation at specific sites affects tau self-assembly, finding that S396 and S400 phosphorylation promotes aggregation while T403 and S404 phosphorylation suppresses it, with pS400 forming a CTE protofilament structure.

This study identifies a conserved leucine in the C-terminus of proteasome activators as essential for gate opening of the human 20S proteasome, with structural and functional evidence supporting its role.

This study reveals the structural basis of electron transfer in the human inducible NOS holoenzyme complex using cryo-EM, showing how cofactors are arranged for catalysis.

This study identifies distinct tau filament structures in FTLD-tau caused by the MAPT S305I mutation, revealing a unique 4-layer architecture and potential RNA-like polyanion binding.

The paper designs synthetic tau fibrils that mimic AD and CTE structures, showing strong seeding ability and catalytic effects in vitro and in cells.

This study determines the structures of CHIP stabilized by Fab antibodies, revealing conformational switches that regulate its E3 ligase and chaperone functions.

This paper identifies design principles for modifying Hsp104 to enhance its therapeutic potential by tuning its collaboration with Hsp70 and Hsp40.

The paper determines the structure of a novel α-synuclein filament fold in multiple system atrophy using cryo-EM, identifying a new filament type distinct from other synucleinopathies.

This study identifies polyphosphate as the 'mystery density' in α-synuclein fibrils by showing it binds to lysine residues, affecting fibril formation and toxicity.

The paper uses cryo-EM to show that tau filaments in Down syndrome share the same structure as those in Alzheimer's disease.