1.B.22 The Outer Bacterial Membrane Secretin (Secretin) Family

The Secretin family consists of a group of Gram-negative bacterial outer membrane proteins that form multimeric pores through which macromolecules, usually proteins, but also filamentous phage can be secreted (Bitter et al., 1998; Cornelis et al., 1998; Hu et al., 1998; Korotkov et al. 2011). These proteins form homomultimeric ring structures, with large central pores (inner diameters of ~5 nm). The pores are plugged, and consequently conductance through secretin pores is minimal. Two secretins, PilQ of Neisseria meningitidis, and PulD of Klebsiella oxytoca are dodecamers with 12 or 14 identical subunits arranged in a ring (Collins et al., 2001, 2003; Linderoth et al., 1997). Secretin phylogeny has been studied by Nguyen et al. (2000) and Clock et al. (2008).  At least some secretins are constitutively in a partially open state (Disconzi et al. 2014).

Secretins are large proteins (420-750 amino acyl residues) consisting of two domains: an N-terminal periplasmic domain (the first 280 residues of XcpQ) and a C-terminal 'homology' domain that is embedded in the outer membrane (residues 283-568 in XcpQ). The C-terminal 'homology' domains of secretins are exclusively responsible for channel formation (Brok et al., 1999) but also includes the central disc and the plug (Chami et al., 2005). The C-domain penetrates both the peptidoglycan on the periplasmic side and the lipopolysaccharide and capsule layers on the cell surface (Chami et al., 2005). A C-terminal S-domain interacts with pilotin, a protein that facilitates secretin targeting to the outer membrane. Secretin subunits, containing multiple domains, interact with numerous other proteins, including secretion-system partner proteins and exoproteins. Features common to all secretins include a cylindrical arrangement of 12-15 subunits, a large periplasmic vestibule with a wide opening at one end and a periplasmic gate at the other (Korotkov et al., 2011).

Secretins function in type II protein secretion (TC #3.5; McLaughlin et al. 2012) (e.g., PulD of Klebsiella oxytoca), type III protein secretion (TC #3.6) (e.g., the hypersensitivity response secretin (HrpH) of Pseudomonas syringiae and the invasion protein secretin (InvG) of Salmonella typhimurium), competence (competence protein E (ComE) of Haemophilus influenzae), fimbrial protein export and assembly (e.g., the fimbrial assembly protein (PilQ) of Pseudomonas aeruginosa), phage assembly (e.g., the gene IV protein of bacteriophage f1), and filamentous phage secretion (Linderoth et al., 1997; Martinez et al., 1998; Nguyen et al., 2000). In Vibrio cholerae, the secretin of the type III secretion system, EpsD, which exports cholera toxin, also exports the filamentous phage, CTXQ, the genome of which encodes cholera toxin (Davis et al., 2000; Marciano et al., 1999). Filamentous phage are secreted and assembled with coat proteins simultaneously. The enteropathogenic E. coli secretin, BfpB, exports pilin subunits and several EPEC proteins, and renders cells sensitive to the antibiotic, vancomycin (Schmidt et al., 2001). Secretins are also found in TC Family 9.A.47 (The Tight Adherens (Pilus) Biogenesis Apparatus)). 

The PilQ DNA competence secretin complex (3.A.11.1.3) is 15 nm wide and 34 nm long and consists of a stable 'cone' and 'cup' five ring structure with a large central channel (Burkhardt et al., 2011). The individual rings are formed by conserved domains of alternating α-helices and β-sheets. The PilQ complex spans the entire cell periphery of T. thermophilus, consistent with the hypothesis that PilQ accommodates a PilA4 comprising pseudopilus, mediating DNA transport across the outer membrane and periplasmic space in a single-step process (Burkhardt et al., 2011).