R. Hartmann-Petersen

A mutational atlas for Parkin proteostasis

This study maps Parkin missense variants' abundance and degradation mechanisms, showing most low-abundance variants are degraded via the ubiquitin-proteasome system and stabilized at lower temperatures.

Characterizing glucokinase variant mechanisms using a multiplexed abundance assay

The paper characterizes mechanisms of human glucokinase variants by analyzing their abundance and stability, identifying residues that affect metabolic stability and conformational dynamics.

Rare catechol-O-methyltransferase (COMT) missense variants are structurally unstable proteasome targets

The paper shows two rare COMT missense variants are structurally unstable, leading to proteasomal degradation and reduced enzyme levels, with degradation independent of COMT isoform.

Lysine deserts prevent adventitious ubiquitylation of ubiquitin-proteasome components

The paper identifies lysine deserts in UPS proteins and shows that introducing lysines increases ubiquitylation, with functional consequences for protein stability and function.

Deciphering the alphabet of disorder -- Glu and Asp act differently on local but not global properties

This study compares the functional and structural differences between glutamate and aspartate in intrinsically disordered proteins using experimental and computational methods.

Discovering functionally important sites in proteins

This paper introduces a machine learning method to predict functional sites in proteins by integrating sequence conservation and biophysical stability models, validated through experimental data on missense variants.

Conserved degronome features governing quality control-associated proteolysis

The paper identifies conserved degron features in yeast, viruses, and humans that govern quality control proteolysis, showing transmembrane domain-like sequences are key determinants of protein half-life.

HSP70-binding motifs function as protein quality control degrons

The paper shows that Hsp70-binding motifs can function as PQC degrons, targeting misfolded proteins for degradation in yeast and human cells.

An amphipathic and cationic antimicrobial peptide kills colistin resistant Gram-negative pathogens in vivo

This paper demonstrates that the cationic amphipathic peptide ChIP effectively kills colistin-resistant Gram-negative pathogens in vivo.

Disease-linked mutations trigger exposure of a protein quality control degron in the DHFR protein

The paper identifies two PQC degrons in DHFR that become exposed in disease-linked missense variants, leading to proteasomal degradation.

Understanding the origins of loss of protein function by analyzing the effects of thousands of variants on activity and abundance

The paper analyzes variant effects on protein activity and abundance in NUDT15 and PTEN, finding that a third of variants cause loss of function and half of these also reduce abundance.

Evolutionarily conserved chaperone-mediated proteasomal degradation of a disease-linked aspartoacylase variant

This study investigates the degradation pathway of a disease-linked ASPA variant, finding it is degraded via the proteasome and dependent on Hsp70 and Hsp110.

Computational and cellular studies reveal structural destabilization and degradation of MLH1 variants in Lynch syndrome

The paper identifies structural destabilization and degradation of MLH1 variants in Lynch syndrome, linking reduced cellular levels to loss-of-function and suggesting stability predictions for diagnostic use.

Classifying disease-associated variants using measures of protein activity and stability

The paper classifies PTEN missense variants as pathogenic or benign using experimental and computational methods, finding that ~60% of pathogenic variants destabilize the protein.