Mechanisms of Membrane-Protein Insertion at the Inner and Outer Membranes

Abstract

For nearly all membrane proteins, insertion into a membrane is not direct, but rather is assisted by other proteins. At the inner membrane, the key element is a protein-conducting channel, the SecY/Sec61 complex. This channel provides a lateral exit into the bilayer while simultaneously offering a pathway into the periplasm. Now, using molecular dynamics flexible fitting (MDFF), we have determined new structures of inactive and active SecY-ribosome complexes. The latter structure reveals in detail how the nascent chain enters the channel, forming loops both above and below it, with the signal anchor intercalated at the open lateral gate. Although bacterial outer-membrane (OM) proteins must first transit SecY into the periplasm, they are inserted via the BamA complex that resides in the OM. Simulations of recently solved crystal structures of BamA suggest that it also opens laterally to the membrane, which has led to the development of a dynamical model for BamA-assisted insertion that is similar in many respect to SecY-mediated insertion.