Outer membrane hemagglutinin secretion protein, FhaC. Functionally important conserved motifs have been identified (Delattre et al., 2010).  The x-ray structure reveals a beta-barrel pore obstructed by two structural elements conserved in all two partner secretion systems, an N-terminal α-helix and an extracellular loop.  FhaC goes from the closed to the open state in the presence of the filamentous haemagglutinin adhesin, FHA.  The N-terminal α-helix is displaced into the periplasm during FHA secretion (Guérin et al. 2014).  With two POTRA domains in the periplasm, a transmembrane beta barrel and a large loop harboring a functionally important motif, FhaC epitomizes the conserved features of the superfamily (Jacob-Dubuisson et al. 2009). The conserved secretion domain of FHA interacts with the POTRA domains, specific extracellular loops and strands of FhaC and the inner beta-barrel surface. The interaction map indicates a funnel-like pathway, with conformationally flexible FHA entering the channel in a non-exclusive manner and exiting along a four-stranded beta-sheet at the surface of the FhaC barrel. This sheet of FhaC guides the secretion domain of FHA along discrete steps of translocation and folding (Baud et al. 2014).  The membrane-proximal POTRA domain exists in several conformations, and the binding of FHA displaces this equilibrium (Guérin et al. 2015). TpsB (Two Partner Secretion) transporters belong to the Omp85 or OMPPI superfamily, whose members catalyze protein insertion into, or translocation across membranes. They are composed of a transmembrane β barrel preceded by two periplasmic POTRA domains that bind the incoming protein substrate. Sicoli et al. 2022 detected minor states in heterogeneous populations, identifying transient conformers of FhaC. This revealed substantial, spontaneous conformational changes on a slow time scale, with parts of the POTRA2 domain approaching the lipid bilayer and the protein's surface loops. An amphipathic POTRA2 β hairpin inserts into the β barrel, and these motions enlarge the channel to initiate substrate secretion. This shows how TpsB transporters mediate protein secretion without the need for cofactors, by utilizing intrinsic protein dynamics (Sicoli et al. 2022).