Efficient farnesylation of an extended C-terminal C(x)3X sequence motif expands the scope of the prenylated proteome
| Autor: | Meet Patel, William P. Saunders, Melanie J. Blanden, Walter K. Schmidt, Daniel S. Hardgrove, Kiall F. Suazo, James L. Hougland, Emily R. Hildebrandt, Mark D. Distefano |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Models
Molecular Proteomics 0301 basic medicine Saccharomyces cerevisiae Proteins Recombinant Fusion Proteins Farnesyltransferase Amino Acid Motifs Green Fluorescent Proteins Protein Prenylation Saccharomyces cerevisiae Biochemistry Substrate Specificity 03 medical and health sciences Prenylation Genes Reporter Animals Humans Enzyme Inhibitors Databases Protein Molecular Biology Alkyl and Aryl Transferases biology Chemistry C-terminus Cell Biology Rats Protein Subunits HEK293 Cells 030104 developmental biology Microscopy Fluorescence Proteome Enzymology Protein geranylgeranyltransferase type I biology.protein Protein farnesylation Protein prenylation Sequence motif |
| Zdroj: | Journal of Biological Chemistry. 293:2770-2785 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m117.805770 |
| Popis: | Protein prenylation is a post-translational modification that has been most commonly associated with enabling protein trafficking to and interaction with cellular membranes. In this process, an isoprenoid group is attached to a cysteine near the C terminus of a substrate protein by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase type I or II (GGTase-I and GGTase-II). FTase and GGTase-I have long been proposed to specifically recognize a four-amino acid CAAX C-terminal sequence within their substrates. Surprisingly, genetic screening reveals that yeast FTase can modify sequences longer than the canonical CAAX sequence, specifically C(x)(3)X sequences with four amino acids downstream of the cysteine. Biochemical and cell-based studies using both peptide and protein substrates reveal that mammalian FTase orthologs can also prenylate C(x)(3)X sequences. As the search to identify physiologically relevant C(x)(3)X proteins begins, this new prenylation motif nearly doubles the number of proteins within the yeast and human proteomes that can be explored as potential FTase substrates. This work expands our understanding of prenylation's impact within the proteome, establishes the biologically relevant reactivity possible with this new motif, and opens new frontiers in determining the impact of non-canonically prenylated proteins on cell function. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|