2.A.103 The Bacterial Murein Precursor Exporter (MPE) Family
Members of the MPE family are found in a large variety of Gram-negative and Gram-positive bacteria . They consist of 370-420 amino acyl residues with 9 (RodA) or 10 (FtsW) putative transmembrane α-helical spanners. Experimental evidence for a 10 TMS model has been reported for FtsW of Streptococcus pneumoniae (Gérard et al., 2002). The S. pneumoniae protein has both its N- and C-termini in the cytoplasm, a large (~60 residue) cytoplasmic domain between TMSs 4 and 5, and a large (~80 residue) extracytoplasmic loop between TMSs 7 and 8.
The best characterized members of the family are the FtsW cell division protein, the RodA rod shape determining protein (both of E. coli) and the SpoVE protein of B. subtilis (Boyle et al. 1997; Errington, 2003; Matsuzawa et al., 1989; Sato et al., 1990). They have been shown to function in the translocation (export) of lipid-linked murein precursors such as NAG-NAM-pentapeptide pyrophosphoryl undecaprenol (lipid II) (Mohammadi et al. 2014). They interact with murein synthases as well as two transpeptidases (PBP2 and PBP3). In Gram-negative bacteria the ftsW gene is physically linked to murG (TC# 9.B.146) which is responsible for the final cytoplasmic step in the synthesis of lipid II before it is flipped to the periplasmic side of the membrane. They may therefore be part of a tunneling device directing the flow of murein precursors to the membrane enzymes that insert the precursors into the preexisting murein sacculus.
Bacterial cell growth necessitates synthesis of peptidoglycan. Assembly of peptidoglycan is a multistep process starting in the cytoplasm and ending in the exterior cell surface. The intracellular part of the pathway results in the production of the membrane-anchored cell wall precursor, Lipid II. After synthesis, this lipid intermediate is translocated across the cell membrane. The translocation (flipping) step of Lipid II requires a specific protein (flippase). Mohammadi et al. (2011) showed that the integral membrane protein FtsW, an essential protein for cell division, is a transporter of the lipid-linked peptidoglycan precursors across the cytoplasmic membrane. Using E. coli membrane vesicles, they found that transport of Lipid II requires the presence of FtsW, and purified FtsW induced the transbilayer movement of Lipid II in model membranes.
The E. coli FtsW and peptidoglycan synthase, PBP3, form a subcomplex (Derouaux et al., 2008; Fraipont et al., 2011; Maggi et al., 2008). The same is observed for SpoVE and SpoVD sporulation proteins in B. subtilis (Fay et al., 2010). Interaction networks (interactomes) have also been identified in Synechocystis strain PCC6803 (Marbouty et al., 2009) and Streptococcus pneumoniae (Maggi et al., 2008). A large complex involving RodA and the cytoskeletal ring in E. coli has been identified (Uehara and Park, 2008; Vats et al., 2009).
The reaction catalyzed by the proteins of the MPE family is:
Lipid-linked murein precursor (in) → Lipid-linked murein precursor (out).