E. Tse

Rampant transcription replication conflict creates therapeutic vulnerability in extrachromosomal DNA containing cancers

This paper identifies transcription-replication conflict as a vulnerability in ecDNA-containing cancers and demonstrates that CHK1 inhibition selectively kills these tumors.

CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis

The paper uses CRISPR screens in iPSC-derived neurons to identify factors controlling tau aggregation, finding new pathways and potential therapeutic targets for tauopathies.

The p97/VCP adapter UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions

This study identifies UBXD1 as a p97 ATPase inhibitor and shows how its domains induce structural remodeling and ring opening of the p97 hexamer.

Asymmetric apical domain states of mitochondrial Hsp60 coordinate substrate engagement and chaperonin assembly

The paper determines cryo-EM structures of a mtHsp60 mutant to show how apical domains coordinate client engagement and chaperonin assembly during the ATP-dependent cycle.

Human Liver Organoids as a Patient-derived Model for HBV Infection and Cellular Response

This paper develops a liver organoid model to study HBV infection and antiviral responses, showing it supports the full HBV lifecycle and can assess drug and immunomodulator effects.

Stacked binding of a small molecule PET tracer to Alzheimer's tau paired helical filaments

The paper determines the cryo-EM structure of GTP-1 bound to Alzheimer's tau filaments, revealing a stacked binding arrangement and favorable pi-pi interactions.

Unique structural features govern the activity of a human mitochondrial AAA+ disaggregase, Skd3.

The paper reports the structure of Skd3-substrate complex, revealing its dodecamer formation and mechanism of protein disaggregation, with implications for SCN and MGCA7.

Structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client-maturation state

The paper determines the cryo-EM structure of the Hsp90:FKBP51:p23 complex, revealing how cochaperones recognize Hsp90 during client maturation.

PIKfyve inhibition blocks endolysosomal escape of α-synuclein fibrils and spread of α-synuclein aggregation

The paper identifies PIKfyve inhibition as a strategy to block α-synuclein fibril escape from lysosomes, reducing aggregation spread in a human cell model.

Practical considerations for using K3 cameras in CDS mode for high-resolution and high-throughput single particle cryo-EM

This study optimizes K3 camera settings in CDS mode for cryo-EM, showing improved resolution and throughput for protein complex imaging.

Conformational Plasticity of the ClpAP AAA+ Protease Couples Protein Unfolding and Proteolysis

This study determines high-resolution structures of E. coli ClpAP complex in substrate-bound states to elucidate the mechanism of protein unfolding and proteolysis coupling.

Compromised function of the ESCRT pathway promotes endolysosomal escape of tau seeds and propagation of tau aggregation

The paper identifies ESCRT pathway components as regulators of tau aggregation propagation by enabling endolysosomal escape of tau seeds.

Mechanistic Insights into the Protective Roles of Polyphosphate Against Amyloid Cytotoxicity

This study investigates how polyphosphate (polyP) affects α-synuclein fibril formation and cytotoxicity, finding that polyP alters fibril morphology and reduces membrane interaction, suggesting potential therapeutic applications.

Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase

The paper determines the cryo-EM structure of a hyperactive ClpB variant bound to casein and ATPγS to elucidate its substrate gripping and translocation mechanism.