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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).


References associated with 2.A.103 family:

Boyle, D.S., M.M. Khattar, S.G. Addinall, J. Lutkenhaus, and W.D. Donachie. (1997). ftsW is an essential cell-division gene in Escherichia coli. Mol. Microbiol. 24: 1263-1273. 9218774
Bush, M.J., N. Tschowri, S. Schlimpert, K. Flärdh, and M.J. Buttner. (2015). c-di-GMP signalling and the regulation of developmental transitions in streptomycetes. Nat. Rev. Microbiol. 13: 749-760. 26499894
Derouaux, A., B. Wolf, C. Fraipont, E. Breukink, M. Nguyen-Distèche, and M. Terrak. (2008). The monofunctional glycosyltransferase of Escherichia coli localizes to the cell division site and interacts with penicillin-binding protein 3, FtsW, and FtsN. J. Bacteriol. 190: 1831-1834. 18165305
Errington, J. (2003). The bacterial actin cytoskeleton. ASM News 69: 608-614. 0
Fraipont, C., S. Alexeeva, B. Wolf, R. van der Ploeg, M. Schloesser, T. den Blaauwen, and M. Nguyen-Distèche. (2011). The integral membrane FtsW protein and peptidoglycan synthase PBP3 form a subcomplex in Escherichia coli. Microbiology 157: 251-259. 20847002
Gérard, P., T. Vernet, and A. Zapun. (2002). Membrane topology of the Streptococcus pneumoniae FtsW division protein. J. Bacteriol. 184: 1925-1931. 11889099
Maggi, S., O. Massidda, G. Luzi, D. Fadda, L. Paolozzi, and P. Ghelardini. (2008). Division protein interaction web: identification of a phylogenetically conserved common interactome between Streptococcus pneumoniae and Escherichia coli. Microbiology 154: 3042-3052. 18832310
Marbouty, M., K. Mazouni, C. Saguez, C. Cassier-Chauvat, and F. Chauvat. (2009). Characterization of the Synechocystis strain PCC 6803 penicillin-binding proteins and cytokinetic proteins FtsQ and FtsW and their network of interactions with ZipN. J. Bacteriol. 191: 5123-5133. 19542290
Matsuzawa, H., S. Asoh, K. Kunai, K. Muraiso, A. Takasuga, and T. Ohta. (1989). Nucleotide sequence of the rodA gene, responsible for the rod shape of Escherichia coli: rodA and the pbpA gene, encoding penicillin-binding protein 2, constitute the rodA operon. J. Bacteriol. 171: 558-560. 2644207
Mohammadi T., Sijbrandi R., Lutters M., Verheul J., Martin NI., den Blaauwen T., de Kruijff B. and Breukink E. (2014). Specificity of the transport of lipid II by FtsW in Escherichia coli. J Biol Chem. 289(21):14707-18. 24711460
Mohammadi, T., V. van Dam, R. Sijbrandi, T. Vernet, A. Zapun, A. Bouhss, M. Diepeveen-de Bruin, M. Nguyen-Distèche, B. de Kruijff, and E. Breukink. (2011). Identification of FtsW as a transporter of lipid-linked cell wall precursors across the membrane. EMBO. J. 30: 1425-1432. 21386816
Sato, T., G. Theeragool, T. Yamamoto, M. Okamoto, and Y. Kobayashi. (1990). Revised nucleotide sequence of the sporulation gene spoVE from Bacillus subtilis. Nucleic Acids Res 18: 4021. 2115675
Sham, L.T., E.K. Butler, M.D. Lebar, D. Kahne, T.G. Bernhardt, and N. Ruiz. (2014). Bacterial cell wall. MurJ is the flippase of lipid-linked precursors for peptidoglycan biogenesis. Science 345: 220-222. 25013077
Uehara, T. and J.T. Park. (2008). Growth of Escherichia coli: significance of peptidoglycan degradation during elongation and septation. J. Bacteriol. 190: 3914-3922. 18390656
Young, K.D. (2014). Microbiology. A flipping cell wall ferry. Science 345: 139-140. 25013047