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Download fileProtein Farnesyltransferase Catalyzes Unanticipated Farnesylation and Geranylgeranylation of Shortened Target Sequences
journal contribution
posted on 10.03.2020, 13:17 authored by Sudhat Ashok, Emily R. Hildebrandt, Colby S. Ruiz, Daniel S. Hardgrove, David W. Coreno, Walter K. Schmidt, James L. HouglandProtein
prenylation is a posttranslational modification involving
the attachment of a C15 or C20 isoprenoid group to a cysteine residue
near the C-terminus of the target substrate by protein farnesyltransferase
(FTase) or protein geranylgeranyltransferase type I (GGTase-I), respectively.
Both of these protein prenyltransferases recognize a C-terminal “CaaX”
sequence in their protein substrates, but recent studies in yeast-
and mammalian-based systems have demonstrated FTase can also accept
sequences that diverge in length from the canonical four-amino acid
motif, such as the recently reported five-amino acid C(x)3X motif. In this work, we further expand the substrate scope of FTase
by demonstrating sequence-dependent farnesylation of shorter three-amino
acid “Cxx” C-terminal sequences using both genetic and
biochemical assays. Strikingly, biochemical assays utilizing purified
mammalian FTase and Cxx substrates reveal prenyl donor promiscuity
leading to both farnesylation and geranylgeranylation of these sequences.
These findings expand the substrate pool of sequences that can be
potentially prenylated, further refine our understanding of substrate
recognition by FTase and GGTase-I, and suggest the possibility of
a new class of prenylated proteins within proteomes.
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Keywords
posttranslational modificationsubstrate scopeC 20 isoprenoid groupsubstrate poolFTaseShortened Target Sequences Protein prenylationprotein substratesCxx substratessequence-dependent farnesylationsubstrate recognitiontarget substrateprotein geranylgeranyltransferase typeC 15protein farnesyltransferaseprenyl donor promiscuitymammalian-based systemsprotein prenyltransferasesprenylated proteinscysteine residueProtein Farnesyltransferase Catalyzes Unanticipated Farnesylationcanonical four-amino acid motif