The prenylation reaction occurs at which region of the protein?
Protein prenylation attaches hydrophobic isoprenoid to facilitate membrane association and protein-protein interactions. Substrate determinant is C-terminal CAAX box where C is cysteine acceptor, A aliphatic amino acids isoleucine, leucine, valine, X residue determining enzyme specificity methionine, serine, glutamine for farnesyltransferase versus leucine for geranylgeranyltransferase I, while Rab proteins contain CC, CXC motifs recognized by geranylgeranyltransferase II. Reaction catalyzed by cytosolic heterodimeric transferases FTase, GGTase I, GGTase II using farnesyl or geranylgeranyl pyrophosphate, forming thioether linkage to cysteine sulfur at extreme carboxyl terminus. After prenylation, endoplasmic reticulum enzymes RCE1 protease removes AAX tripeptide and ICMT methyltransferase methylates newly exposed carboxyl enhancing hydrophobicity. Therefore prenylation occurs at C-terminal cysteine, not N-terminal glycine characteristic of myristoylation nor internal serine which undergoes O-phosphorylation or O-GlcNAcylation. This C-terminal lipidation positions Ras, Rho, Rab, lamins at appropriate membranes including plasma membrane, endosome and nuclear envelope for functional signaling. 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.
Ref: Zhang & Casey, Annu Rev Biochem 1996, CAAX prenylation; Wang & Casey, Nat Rev Mol Cell Biol 2016.