Transmembrane Domain Recognition during Membrane Protein Biogenesis and Quality Control.

One-fourth of eukaryotic genes code for integral membrane proteins, nearly all of which are inserted and assembled at the endoplasmic reticulum (ER). The defining feature of membrane proteins is one or more transmembrane domains (TMDs). During membrane protein biogenesis, TMDs are selectively recognized, shielded, and chaperoned into the lipid bilayer, where they often assemble with other TMDs. If maturation fails, exposed TMDs serve as a cue for engagement of degradation pathways. Thus, TMD-recognition factors in the cytosol and ER are essential for membrane protein biogenesis and quality control. Here, we discuss the growing assortment of cytosolic and membrane-embedded TMD-recognition factors, the pathways within which they operate, and mechanistic principles of recognition.