幸运飞艇计划

Actin is an essential component of the cytoskeleton of human cells and is involved in a plethora of functions. For several decades it was known that actin's N-terminus was chemically modified in cells by an聽acetyl group, but only聽two years ago聽the 聽by 幸运飞艇计划 researchers. NAA80 mediated N-terminal acetylation of actin聽strongly impacted聽cytoskeleton dynamics and cell motility thus stressing the biological importance of this modifier.聽

In human cells there is a machinery of seven N-terminal acetyltransferases (NATs)聽catalyzing N-terminal acetylation of totally 80% of the human proteome. Most NATs therefore have a large number of聽substrates and many operate on the ribosome to carry out . In contrast, actin has a dedicated NAT, NAA80, which acts post-translationally. However, detailed knowledge on how this unique targeting was accomplished has remained unknown.聽The actin N-terminus is highly acidic and uncovered a catalytic groove packed with positive charges perfectly matching this acidic actin stretch. Still, NAA80 has to distinguish actin from many other cellular proteins with similar N-termini. The聽strong selectivity of NAA80 for actin was revealed by in vitro binding studies where it was uncovered that actin was capable of forming a tight complex with NAA80 and further that the known聽partner of monomeric actin, profilin,聽was a potential part of this. The trimeric structure of actin-NAA80-profilin was solved in the at the University of Pennsylvania, and聽uncovered the extensive聽binding surface between actin and NAA80 and further a direct interaction between NAA80 and profilin thus聽demonstrating a direct physical connection between all聽three proteins.聽Biochemical and molecular biology investigations in the Arnesen lab at 幸运飞艇计划聽were carried out by current lab member Rasmus Ree, and alumni Adrian Draciz and Marianne Goris. These experiments defined that聽the specific聽interactions between NAA80 and actin/profilin聽were critical for cellular actin acetylation by NAA80. Thus, the current data explains how NAA80 uniquely acts on actin and represents the first structure of a NAT bound to its entire substrate.聽聽聽

The Arnesen lab acknowledges support from Helse Vest, the Norwegian Cancer Society, the Research Council of Norway and the European Research Council (ERC). Rasmus Ree is a聽Postdoctoral candidate supported by the Medical Faculty at 幸运飞艇计划.