Practice question

Selective inclusion of membrane cargo into COPII vesicles instead of bulk flow relies on export signals recognized directly by Sec24 adaptor subunit. Well-characterized ER export code is di-acidic DXE motif positioned four to ten residues downstream of transmembrane domain in cytosolic C-terminal tails of many type I proteins like VSV-G, Sys1, ERGIC-53, SNAREs Bet1, Sec22. Motif consists of Asp-X-Glu where both acidic side chains fit basic pockets formed by arginine and lysine in Sec24 B-site; upstream hydrophobic aromatic residues strengthen interaction. Crystal structures show Sec24C and Sec24D isoforms especially adept binding DXE while Sec24A-B prefer IxM signals. Mutation of DXE to AXA drastically lowers affinity slowing ER exit five to ten fold causing ER retention and degradation. KKXX at extreme C-terminus binds alpha beta prime COP I subunits for Golgi-to-ER retrieval opposite direction. Tyrosine-based YXXPhi recognized by mu subunit of AP complexes for clathrin-mediated TGN to endosome and plasma membrane endocytosis, NPXY recognized by PTB domains of Dab2 and ARH for LDL receptor uptake. Thus DXE uniquely encodes ER exit into COPII for anterograde traffic ensuring efficient export.