1.A.34 The Bacillus Gap Junction-like Channel-forming Complex (GJ-CC) Family
SpoIIQ and SpoIIIAH (See 9.B.70.1.1) have been reported to form a channel connecting the B. subtilis mother cell to the pre-forespore. SpoIIIAA-AH are encoded within a single operon and may function as a protein secretion system. SpoIIQ and SpoIIAA-AH are produced in the mother cell under σE control and are normally required for activation of σG in the forespore by σE in the mother cell. Possibly these two proteins form a channel linking the two compartments of the Bacillus sporangium (Camp and Losick, 2008).
Meisner et al., 2008 showed that SpoIIIAH is targeted to the forespore membrane. Both SpoIIIAH (218 aas) and SpoIIQ (283 aas) have single N-terminal TMSs with the bulk of the protein on the outside. They have affinity for each other in their extracytoplasmic domains. Consquently they may abut each other to form a trans 2-membrane pore, allowing the mother cell to feed and signal to the forespore. The pore appears to be large enough to transport small molecules but not proteins.
SpoIIIAH is similar to YscJ/FliF of the type III and flagellar systems (TC#3.A.6) of enteric bacteria, and like them, forms ring structures (Meisner et al., 2008). Camp and Losick, 2009 have suggested that the channel formed by SpoIIQ and SpoIIIAH is like a ''feeding tube'', like a gap junction of animal cells (see also Kroos, 2009).
Meisner et al. (2012) reported a 2.8-Ã… resolution structure of a complex of SpoIIQ and SpoIIIAH. SpoIIIAH folds into the ring-building structural motif, and modeling shows that the structure of the SpoIIQ-SpoIIIAH complex is compatible with forming a symmetrical oligomer that is similar to those in type III protein secretion systems (3.A.6). The inner diameters of the two most likely ring models are large enough to accommodate several copies of other integral membrane proteins. SpoIIQ contains a LytM domain, which is found in metalloendopeptidases, but lacks residues important for metalloprotease activity. Other LytM domains appear to be involved in protein-protein interactions. Meisner et al. (2012) found that the LytM domain of SpoIIQ contains an accessory region that interacts with SpoIIIAH.
The Bacillus SpoIIQ/SpoIIIAH transcompartment channel interconnects the forespore and the mother cell. The activity of sigmaG requires this channel apparatus through which the adjacent mother cell provides substrates that generally support gene expression in the forespore. Flanagan et al. 2016 reported that SpoIIQ is bifunctional, specifically maximizing sigmaG activity as part of a regulatory circuit that prevents sigmaG from activating transcription of the gene encoding its own inhibitor, the anti-sigma factor CsfB.
The SpoIIQ/SpoIIIAH complex of Bacillus subtilis
SpoIIQ homologue of one of the two components (SpoIIQ and SpoIIIAH) of the gap junction-like channel-forming complex of B. subtilis. Several SpoIIQ homologues in various E. coli strains were identified, but no homologue of the SpoIIAH component was found. Therefore, pore formation can not be inferred.
SpoIIQ homologue of E. coli
Uncharacterized metaloprotease family M23 of 245 aas. Shows sequence similarity to SpoIIQ in an 80 residue region, residues 140 - 220 in both proteins.
UP of E. coli
SpoIIQ-SpoIIIAH complex spanning the two membranes of the mother cell and the prespore. Inhibiting SpoIIQ, SpoIIIAA, or SpoIIIAH function apparently prevents the formation of infectious C. difficile spores and thus disease transmission (Fimlaid et al. 2015). spoIIQ or spoIIIAH mutants that complete engulfment are impaired in post-engulfment, forespore and mother cell-specific gene expression, in agreement with a channel-like function (Serrano et al. 2016).
SpoIIQ-SpoIIIAH of Clostridium difficile
SpoIIQ, 222 aas and 1 N-terminal TMS
SpoIIIAH, 229 aas and 1 N-terminal TMS