The trans-envelope architecture and function of the type 2 secretion system: new insights raising new questions.

Nanomachines belonging to the type IV filament (Tff) superfamily serve a variety of cellular functions in prokaryotes, including motility, adhesion, electrical conductance, competence and secretion. The type 2 secretion system (T2SS) Tff member assembles a short filament called pseudopilus that promotes the secretion of folded proteins from the periplasm across the outer membrane of Gram-negative bacteria. A combination of structural, biochemical, imaging, computational and in vivo approaches had led to a working model for the assembled nanomachine. High-resolution cryo-electron microscopy and tomography provided the first view of several homologous Tff nanomachines in the cell envelope and revealed the structure of the outer membrane secretin channel, challenging current models of the overall stoichiometry of the T2SS. In addition, recent insights into exoprotein substrate features and interactions with the T2SS have led to new questions about the dynamics of the system and the role of the plasma membrane in substrate presentation. This micro-review will highlight recent advances in the field of type 2 secretion and discuss approaches that can be used to reach a mechanistic understanding of exoprotein recognition, integration into the machine and secretion.