Modifications and Targeting of Protein Termini

Modifications and Targeting of Protein Termini, Volume 684 in the Methods in Enzymology series serial highlights new advances in the field, with this new volume presenting interesting chapters pn a variety of timely topics, including Optimizing purification and activity assays of N-terminal methyltransferase complexes, In vitro reconstitution of hierarchical steps of Arg/N-degron pathway, Identification of N-degrons and N-recognins by using peptide-pull-downs combined with quantitative proteomics, A decoupled Virotrap approach to study the interactomes of N-terminal proteoforms, Monitoring ADO-dependent proteolysis in cells using fluorescent reporter proteins, Site-specific α-N-terminal methylation on peptides through chemical and enzymatic methods, and more.

Additional sections cover Monitoring the interactions between N-degrons and N-recognins of the Arg/N-degron pathway, Characterization and chemical modulation of p62/SQSTM1 as an autophagic N-recognin of the Arg/N-degron pathway, Analysis of higher plant N-degron pathway components and substrates via expression in S. cerevisiae, and so much 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.