Practice question

Membrane protein classification by lipid modification clarifies attachment without transmembrane span. Ras GTPases undergo prenylation by farnesyltransferase recognizing C-terminal CAAX motif, subsequent RCE1 proteolysis, ICMT methylation, and for N-Ras and H-Ras additional Golgi palmitoylation by DHHC enzymes driving plasma membrane targeting and partitioning into ordered domains for MAPK signaling and transformation. Src family kinases c-Src, Fyn, Lck, Yes undergo cotranslational N-myristoylation at glycine two plus reversible S-palmitoylation for stable inner leaflet association recruiting downstream effectors upon receptor activation. GPI-anchored proteins by definition are lipid-linked via glycolipid in outer leaflet providing high mobility. Actin however is forty-two kilodalton globular ATPase forming double-helical F-actin microfilaments comprising cortical cytoskeleton beneath membrane. It associates indirectly via adaptors ankyrin, protein 4.1R, ERM proteins vinculin talin and through phosphatidylinositol 4,5-bisphosphate binding but carries no covalent lipid. Its ATP dependent polymerization dynamics and treadmilling differ fundamentally from lipidation-dependent anchoring mechanisms. Understanding these attachment modes clarifies pharmacological targeting of lipidation enzymes versus actin polymerization inhibitors in signaling and cytoskeletal research.