Practice question

Heterotetrameric adapter protein complexes link cargo sorting signals to clathrin and other coats decoding destinations. AP2 composed of alpha, beta2, mu2, sigma2 about 300 kDa localizes exclusively to plasma membrane where alpha appendage ear binds PIP2 and accessory proteins Eps15 and epsin. Mu2 middle domain recognizes YXXPhi tyrosine signals where tyrosine sits in deep hydrophobic pocket and phi bulky hydrophobic; affinity enhanced by phosphorylation at Thr156 by AAK1 kinase upon membrane recruitment. Dileucine [DE]XXXL[LI] also recognized. Transferrin receptor YTRF, LDL receptor FXNPXY via co-adaptor ARH linking to AP2, and many signaling receptors use this for rapid internalization forming pits 0.5 percent surface. AP1 at TGN and endosomes contains gamma adaptin and mediates TGN to endosome traffic, not Golgi to ER which uses COPI dilysine. AP3 delivers to lysosomes and lysosome-related organelles melanosomes via tyrosine and dileucine; COPII formation depends on Sec24 not AP3. AP complexes use clathrin or related coats; interaction with cargo tails not SNAREs defines sorting specificity bridging membrane, signal, and coat.