Practice question

Farnesylation is post-translational prenylation catalyzed by heterodimeric farnesyltransferase FTase using farnesyl pyrophosphate derived from mevalonate cholesterol biosynthesis pathway as donor. Modification occurs at CAAX motif at extreme C-terminus where C is cysteine, A aliphatic residues, X typically methionine, serine or glutamine directing farnesyl addition versus leucine directing geranylgeranyl addition. Reaction forms thioether bond between cysteine sulfur and C1 of isoprenoid. Farnesyl group is linear 15-carbon isoprene polymer comprising three isoprene units with 3 double bonds providing hydrophobicity for membrane association. After attachment, RCE1 protease removes AAX tripeptide and ICMT methyltransferase methylates terminal carboxylate increasing hydrophobicity. It does not occur at N-terminal glycine like myristoylation, does not use geranylgeranyl precursor for Ras canonical farnesylation, and results in thioether not amide linkage. Ras isoforms require farnesylation for plasma membrane anchoring required for downstream MAPK signaling and oncogenic transformation, target for farnesyltransferase inhibitors. Such detailed mechanistic insight is frequently examined in competitive tests including NEET, CUET, CSIR-NET and GATE where transporter classification, energetics and disease linkage are integrated into problem-solving questions.