Researchers Solve Protein Mystery
Published:18 Jan.2024 Source:The University of Bergen
Proteins are key to all processes in our cells and understanding their functions and regulation is of major importance. One of the most common protein modifications in human cells is N-terminal acetylation, which is an addition of a small chemical group (acetyl) at the starting tip (N-terminus) of a protein. The modification is launched by a group of enzymes called N-terminal acetyltransferases (NATs). Despite being "everywhere" in human cells, the functional role of this modification remains mysterious
To address this question, molecular biologist and researcher Sylvia Varland spent two years at the Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Canada, supported by a FRIPRO mobility grant from the Research Council of Norway. Here, she used the established CRISPR-Cas9 technology and powerful screening platforms available in one of the best scientific environments to define the functional roles of the human NAT enzymes. Sylvia focused on one of the major human NAT enzymes, NatC, and the genome-wide screening of human NatC KO cells revealed many human genes likely to be involved in the function of N-terminal acetylation. N-terminal acetylation has the power to dictate a protein's lifetime and affects our cells in numerous ways
In conclusion, using an unbiased and global genetic screen combined with cellular phenotyping, the team uncovered a general function for N-terminal acetylation in protecting proteins from degradation in human cells. The molecular investigations defined the cellular components (ubiquitin ligases) responsible for degrading a major class of human proteins when lacking N-terminal acetylation. The role of NatC-mediated protection of specific proteins is evident both in human cells and in fruit fly.