Membrane proteins do not simply slip into membranes. Their insertion into the lipid bilayer is an orchestrated process guided by both the sequence of the inserting protein and cellular machinery that catalyzes insertion. We study how transmembrane helices are recognized, oriented, and inserted into the membrane, and how membrane protein sequences have evolved to cooperate with the cellular factors that make this possible.
Our recent work showed that this sequence–machinery match is not just a basic cell-biological principle, but also a vulnerability: disease-associated mutations can disrupt the insertion of transmembrane helices, causing membrane proteins to misfold, mislocalize, or lose function.
