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 protein, which is mainly present in the IM as a homo-oligomer, translocates nascent OMPs across the IM; at the same time, SecA directly interacts with the β-barrel assembly machinery (BAM) complex embedded within the OM. A supercomplex (containing SecA , 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 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 and theoretical structures for the core-complex composed of SecA 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 and the supercomplex function in the biogenesis of OMPs.

© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.