Protein prenylation is a post-translational modification wherein an isoprenoid group is attached to a cysteine residue near the C-terminus of a substrate protein by either farnesyltransferase (FTase) or geranylgeranyltransferase type I (GGTase-I). Biochemical, structural, and computational studies of FTase and GGTase-I have supported the adoption of a “Ca1a2X” C-terminal sequence as a consensus targeting motif for protein prenyltransferase recognition. Yeast genetic screening studies have revealed that yeast FTase can modify sequences that diverge in length from the canonical “Ca1a2X” sequence. Mammalian FTase can also prenylate these "forbidden" seqeunces, with sequences exhibiting sufficient efficiency to support biologically relevant protein farnesylation within the cell. This expansion in prenylation motifs more than doubles the number of proteins within the yeast and human proteomes that can be potentially modified. This work establishes the biological relevance of new prenylation target sequences within cells, expands our understanding of the impact of prenylation within the proteome, and opens a new frontier in determining post-translational modification enzyme selectivity and the impact of these non-canonical prenylated proteins on cell behavior and biological function.

Expanding the scope of the prenylated proteome: Forbidden C-terminal sequences can be efficiently prenylated by protein farnesyltransferase

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.