Membrane protein folding: beyond the two stage model

The folding of a-helical membrane proteins has previously been described using the two stage model, in which the membrane insertion of independently stable a-helices is followed by their mutual interactions within the membrane to give higher order folding and oligomerization. Given recent advances in our understanding of membrane protein structure it has become apparent that in some cases the model may not fully represent the folding process. Here we present a three stage model which gives considerations to ligand binding, folding of extramembranous loops, insertion of peripheral domains and the formation of quaternary structure. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.