Putative role of the POTRA domain.
	The presence of five POTRA repeats in D15 related proteins associated to a -barrel membrane channel and their conservation among Gram-negative bacteria, would suggest that they are also involved in transport process (like ShlB or Toc75 families) and could have a basic function, such as cell envelope biogenesis or outer membrane assembly, still something that has to be demonstrated. From an immunological point of view, peptides derived from the N-terminal half of D15 from Hemophilus influenzae were strongly recognised by the antisera raised against the full-length D15 protein. These results indicated that the N-terminal region of D15 (POTRA repeats 1 to 3) contains most of its immunodominant B-cell epitopes and thus, this region is a potential candidate vaccine [Yang et al 1998].
	The CGI51 family is present in human, fly, worm, yeast and plants [Lai 2000]. They are an experimentally uncharacterised family, but its phylogenetic distribution and the predicted barrel transmembrane C-terminal region, typical of outer membrane proteins [Schulz 2002], suggest that the function of this protein may be related to an uncharacterised mitochondrial transport process [Reichert and Neupert 2002].
	The high sensitivity to trypsin cleavage of inactive ShlA (the ShlB specific export substate) suggests that its secretion-competent conformation is not tightly folded [Yang and Braun 2000]. N-terminal ShlB mutants that uncoupled ShlA secretion from ShlA activation were reported, suggesting  that the POTRA containing fragment of ShlB could have a chaperone-like function over ShlA [Yang and Braun 2000]. POTRA domains could interact with their substrates in a secretion-competent state that is capable of engaging the secretion machinery to travel through the -barrel in an unfolded or partially folded manner, in an analogous way to the bacterial type III secretion SicP chaperone [Stebbins et al. 2001]. This is in agreement with the cork hypothesis, where the domain would fold back into the C-terminal -barrel membrane channel, as observed for the N-terminal domain of FepA [Guedin et al 2000, Buchanan et al 1999], and would explain why N-terminal deletion mutants for ShlB (POTRA domain-containing region), produce channels with a considerably higher single channel conductance, compared with the wild-type protein[Konninger et al 1999].

	FtsQ was initially characterised like essential in bacterial division, their homologous in Gram-positive (DivIB) present this quality only at higher temperatures, but it recently was reported that this DivIB requirement can be suppressed by overexpression of FtsL (another division machinery protein also present in Gram-negative bacteria), indicating that one of the most important roles for DivIB in cell division is in maintaining the stability of FtsL. This led to the hypothesis that FtsQ/DivIB may have a chaperone-like role, protecting FtsL from degradation [Daniel and Errington 2000]. We propose here that this function could be related with the POTRA domain of FtsQ/DivB.

The hypothesis that the POTRA domain could have a chaperone like function creates an evolutionary picture in which, a bacterial ubiquitous domain (POTRA from FtsQ/DivIB family), was incorporated by a class of -barrel outer membrane proteins (ShlB like, characteristic of Gram-negative bacteria) to regulate their channel properties.