Nicholas Gene Brown

High-throughput protein target mapping enables accelerated bioactivity discovery for ToxCast and PFAS compounds

The paper uses high-throughput affinity-selection mass spectrometry to identify protein targets of ToxCast and PFAS compounds, discovering novel interactions and revealing distinct binding patterns of legacy and replacement PFAS.

Structural basis of NSD2 degradation via targeted recruitment of SCF-FBXO22

This paper reveals the structural basis of NSD2 degradation via SCF-FBXO22 recruitment, showing how aldehyde-based degraders induce conformational changes for covalent binding and efficient protein degradation.

Design of linked-domain protein inhibitors of UBE2D as tools to study cellular ubiquitination

This paper designs a protein inhibitor for UBE2D enzymes to study their role in ubiquitination, showing it reduces Ub degradation and proteotoxic stress in HeLa cells.

Domain-specific decoupling of co-chaperone and ligase functions in STUB1 underlies biochemical and clinical heterogeneity in SCA48

This study identifies how STUB1 mutations in SCA48 disrupt co-chaperone and ligase functions in a domain-specific manner, leading to clinical heterogeneity.

Mechanisms of USP18 deISGylation revealed by comparative analysis with its human paralog USP41

This study identifies molecular determinants of USP18's specificity for ISG15 through comparative analysis with its paralog USP41, revealing structural features essential for enzymatic activity.

USP37 prevents unscheduled replisome unloading through MCM complex deubiquitination

This study identifies USP37 as a deubiquitinase that prevents premature replisome disassembly by deubiquitinating MCM7, ensuring genome stability and normal cell cycle progression.

Structural basis for the ubiquitin chain recognition of the human 26S proteasome

The paper determines how the human 26S proteasome distinguishes between K48-linked and K11/K48-branched ubiquitin chains through structural analysis and functional studies.

Phosphorylation-State Modulated Binding of HSP70: Structural Insights and Compensatory Protein Engineering

This study examines how phosphorylation at HSP70 T636 affects its binding to CHIP, showing reduced affinity and altered interactions with other co-chaperones, with implications for disease.

Dosage sensitivity in Pumilio1-related phenotypes reflects distinct disease mechanisms

The paper investigates how different PUM1 mutations lead to distinct phenotypes by analyzing PUM1 interactomes and showing that dosage sensitivity involves non-linear mechanisms.