Modifications and Targeting of Protein Termini

Modifications and Targeting of Protein Termini, Part B, Volume 686 in the Methods in Enzymology serial, highlights new advances in the field with this new volume presenting interesting chapters on a variety of timely topics, including In vitro production of N-degron fused proteins and its application, Identification of N-degrons and N-recognins using peptide pull-downs combined with quantitative mass spectrometry-based proteomics, Monitoring ADO-dependent proteolysis in cells using fluorescent reporter proteins, Monitoring the interactions between N-degrons and N-recognins of the Arg/N-degron pathway, Characterization and chemical modulation of p62/SQSTM1/Sequestosome-1 as an autophagic N-recognin of the Arg/N-degron pathway.

Other chapters cover Analysis of higher plant N-degron pathway components and substrates via expression in S. cerevisiae, Building libraries to dissect terminal degrons with fluorescent timers, Affinity isolation and biochemical characterization of N-degron ligands using the N-recognin, ClpS, Probing the effects of N-terminal acetylation on α-synuclein structure, aggregation and toxicity, Increasing the coverage of the N-terminome with Lys-N Amino Terminal enrichment (LATE), and more.

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Professor Thomas Arnesen received his Ph.D. in molecular biology from the University of Bergen, Norway in 2006. After postdoctoral work at Haukeland University Hospital and University of Rochester Medical Center, he established his own lab at the University of Bergen in 2010. His main interest has been protein N-terminal acetylation and the responsible enzymes, the N-terminal acetyltransferases (NATs). Using Saccharomyces cerevisiae and human cell models combined with in vitro approaches his lab and collaborators have i) identified and defined the presumed complete cytosolic human NAT-machinery including NATs acting post-translationally, ii) quantitatively analysed the N-terminal acetylomes of yeast and human cells, iii) developed novel assays for NAT-profiling, iv) gained mechanistic insights of the molecular and cellular effects of N-terminal acetylation, v) contributed to the understanding of the physiological and clinical importance of NATs by revealing the links between NatA and cancer cell survival and drug sensitisation, and lately by defining genetic disorders caused by pathogenic NAT variants. The Arnesen lab also contributed to solving the first NAT-structures and developing the first potent NAT-inhibitors.

With Fred Sherman and Bogdan Polevoda, Arnesen introduced the NAA (N-alpha acetyltransferase) nomenclature of the N-terminal acetyltransferase genes and proteins, and he acts as the specialist advisor for the HUGO Gene Nomenclature Committee for these genes. Arnesen is one of the founders and council members of the International Society of Protein Termini (ISPT). He has organized several symposia on N-terminal acetylation, and in 2022 he was the head organizer of the EMBO Workshop ‘Protein Termini – From mechanism to biological impact’ in Bergen, Norway. Arnesen has co-authored more than 100 peer-reviewed publications. Today he is head of the Translational Cell Signaling and Metabolism group at the Dept. of Biomedicine, UiB, supported by the Research Council of Norway and ERC. Here his team continues the basic and translational research to understand the impact of protein N-terminal modifications.