Trends in Biochemical Sciences
ReviewSequence-structure relationships in polysaccharide co-polymerase (PCP) proteins
Section snippets
Wzy-dependent polysaccharide biosynthesis
The cell surface polysaccharides produced by bacteria affect the interactions with their environment and, in pathogenic bacteria, contribute to immune avoidance and host–pathogen interactions. The biosynthesis of many lipopolysaccharide (LPS) O-antigens (Oags), enterobacterial common antigen (ECA) and some capsule polysaccharides (CPSs) in Gram-negative and Gram-positive bacteria occurs by a mechanism known as the Wzy polymerase-dependent pathway 1, 2, 3, 4. The process relies on a putative,
PCP proteins
A large number of proteins, in addition to Wzz, can influence the length and/or export of polysaccharides. These have been named PCPs (for polysaccharide co-polymerases) and are further distinguished by their common membrane topology: nearly all harbor transmembrane helices near the N (TM1) and the C (TM2) termini, a periplasmic α-helical domain containing a predicted coiled-coil region and limited conserved sequence motifs including a Pro–Gly-rich segment overlapping TM2 [20]. Residues within
Crystal structures of PCP1 proteins
The structures of the periplasmic domains of the three different PCP1 protomers reveal that, despite their limited sequence identity (21–27%), they all adopt a similar fold that can be divided structurally into two domains, an α-β base domain and a protruding α helical hairpin domain [23] (Figure 1a). The α-β base domain comprises the N-terminal part of the periplasmic region and is located at the bottom of the protomer close to the membrane. A single β-strand at the C terminus, just before the
Structural predictions for other PCP subfamilies
To explore wider structural similarities within the PCP family [20], we have used secondary structure predictions (Figure 2) to analyze representatives of each subfamily and compare them with the atomic resolution structures of PCP1 proteins (Figure 1). E. coli K-12 Wzc and Sinorhizobium meliloti ExoP were chosen as representatives of the PCP2a subfamily. We have also analyzed CpsC from Streptococcus pneumoniae as a member of the PCP2b subfamily and KpsE from E. coli as the representative of
Current model for Wzy-dependent Oag biosynthesis
The recent structural data obtained for Wzz proteins have prompted the proposal of a new model for Wzy-dependent Oag biosynthesis [23]. In this model, a Wzz oligomer serves as a scaffold for Wzy molecules to facilitate Oag polymerization by a mechanism involving the transfer of the growing chain from one Wzy molecule to the next (Figure 3). Different modal lengths would result from the different Wzz protein oligomer sizes, which in turn would determine the number of neighboring Wzy molecules
Concluding remarks and future perspectives
The Wzz proteins provide a striking example of how a common structural template can control the synthesis or length of different polymers, while at the same time promote differences in protein quaternary structure. These PCP1 structures shed a broad light on the entire PCP family, revealing, to a large extent, a similar structural framework in other PCPs. The nature of oligomerization in other PCP families and the functional importance of oligomer formation are key questions that will require
Acknowledgements
Our work is supported in part by the National Research Council of Canada (to M.C. and A.M.), the Canadian Institutes of Health Research (CIHR) grant MOP-48370 (to M.C.) and by an Australian National Health and Medical Research Council Program Grant (to R.M.). This is publication number 49562 from the National Research Council of Canada.
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