Practice question

Glycosylphosphatidylinositol anchoring is complex post-translational modification processed in endoplasmic reticulum for about 150 human proteins destined for extracellular leaflet. Nascent proteins contain C-terminal hydrophobic signal peptide that is recognized by transamidase complex, cleaved after a specific omega residue, and replaced en bloc with preformed GPI moiety consisting of phosphatidylinositol lipid, glucosamine, three mannoses, phosphoethanolamine and galactose modifications. Attachment occurs to new C-terminus via amide linkage between protein carboxyl group and ethanolamine phosphate, positioning glycolipid anchor at extreme carboxyl end. This explains why internal lysine, N-terminus or mid-region attachments are incorrect; GPI always replaces C-terminal signal. Resulting GPI-anchored proteins orient extracellularly in lipid rafts, participating in adhesion, complement regulation, enzymatic activity and signal transduction. Examples include Thy-1, CD59 protectin, DAF, alkaline phosphatase and prion protein, cleavable by GPI-specific phospholipases for regulated shedding. 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.