Structural insights into the mechanism of a novel protein targeting pathway in Gram-negative bacteria

Many nascent polypeptides synthesized in the cytoplasm are translocated across membranes via a specific 'translocon' composed of protein complexes. Recently, a novel targeting pathway for the outer membrane β-barrel proteins (OMPs) in Gram-negative bacteria was discovered. The cell envelope of Gram-negative bacteria is composed of the inner (plasma) membrane (IM) and the outer membrane (OM). In this new pathway, a SecA^N protein, which is mainly present in the IM as a homo-oligomer, translocates nascent OMPs across the IM; at the same time, SecA^N directly interacts with the β-barrel assembly machinery (BAM) complex embedded within the OM. A supercomplex (containing SecA^N , the BAM complex and many other proteins) spans the IM and OM, and is involved in the biogenesis of OMPs. Investigation of the function of SecA^N and the supercomplex, as well as the translocation mechanism, will require elucidation of their structures. However, no such structures are available. Therefore, here, I describe the use of protein modeling to build homology models for SecA^N and theoretical structures for the core-complex composed of SecA^N and the BAM complex, which is a key part of the supercomplex. The modeling data are consistent with previous experimental observations and demonstrated a conformational change of the core-complex. I conclude by proposing mechanisms for how SecA^N and the supercomplex function in the biogenesis of OMPs.