Dissecting the folding mechanism of the outer membrane protein PagP

Introduction The E.coli outer membrane (OM) is densely packed with outer membrane proteins (OMPs) that carry out a diverse range of functions that include (non)specific transport of small and large ligands, proteolytic and synthetic reactions and cellular recognition and adhesion. However, despite their importance, understanding the biogenesis of OMPs and their folding and insertion into membranes is a formidable challenge (Figure 1). For soluble proteins, excellent progress towards answering how the information inherent in the amino acid sequence of a protein enables it to adopt a native, three-dimensional structure has been made by integrating experimental folding studies on small model proteins with computer simulations. By contrast, progress in understanding the folding mechanisms of membrane proteins has been much more limited, in part because of the complexity added to delineating the mechanisms of folding by the membrane environment in which the protein resides.