TCDB is operated by the Saier Lab Bioinformatics Group

8.A.3 The Cytoplasmic Membrane-Periplasmic Auxiliary-1 (MPA1) Protein with Cytoplasmic (C) Domain (MPA1-C or MPA1 C) Family

Proteins of the MPA1-C family, also called the polysaccharide copolymerase (PCP2a) family, have been proposed to function in conjunction with PST porters (TC #2.A.66.2) and polysaccharide polymerases for the polymerization and export of complex polysaccharides (Paulsen et al., 1997). The cytoplasmic (C) domain (the B. subtilis YwqF protein) is a tryrosyl kinase that phosphorylates and activates UDP-glucose dehydrogenase, an essential enzyme for exopolysaccharide synthesis (Mijakovic et al., 2003). This enzyme is activated by the membrane domain/protein, YwqC. Wzc of E. coli also exhibits protein-tyrosine autokinase activity (Vincent et al., 1999). It forms a tetrameric complex required for the assembly of group 1 capsules (Collins et al., 2006).

Mutation of the tyrosyl phosphorylation site of ExoP in S. meliloti changes the ratio of high MW to low MW succinoglycan (Niemeyer and Becker, 2001). In the Streptococcus pneumoniae homologue, CpsD, the tyrosines in the C-terminal (YGX)4 repeats are essential for activity (Morona et al., 2003). Wzb is its cognate phosphotyrosyl protein phosphatase; they are required for the production/assembly of high molecular weight forms of colanic acid capsular polysaccharide. Thus, phosphorylation of Wzc prevents production while Wzb catalyzed dephosphorylation restores production (Vincent et al., 2000). Similarly, autophosphorylation of CpsD of Streptococcus pneumoniae negatively regulates synthesis of capsular polysaccharide (Morona et al., 2000).

The MPA1 proteins span the cytoplasmic membrane twice as putative α-helical spanners and possess large periplasmic ''loop'' domains that might connect the cytoplasmic membrane PST porter with the outer membrane auxiliary (OMA; TC #1.B.18) protein which may exist as an oligomeric β-structure-type pore across the outer membrane, but this postulate has not been substantiated. These proteins function only in exo- or capsular polysaccharide synthesis/export (not in lipopolysaccharide export) in Gram-negative bacteria.

Capsules, protective structures on the surfaces of many bacteria, include almost 80 capsular serotypes in E. coli. Biosynthesis and translocation of capsular polysaccharides to the cell surface are probably temporally and spatially coupled by multiprotein complexes that span the cell envelope (Whitfield 2006). Crystal structures of Wzc, a tyrosyl kinase, and Wzb, a tyrosyl protein-P phosphatase, of E. coli are known (Hagelueken et al. 2009). The cyclic process of auto-phosphorylation of the C-terminal tyrosine cluster of a BY-kinase (Bacterial tyrosine kinase), and its subsequent dephosphorylation following interactions with a counteracting tyrosine phosphatase, regulates diverse physiological processes including biosynthesis and export of polysaccharides responsible for the formation of biofilms or virulence-determining capsules (Temel et al. 2013).

References associated with 8.A.3 family:

Alphonse, S., I. Djemil, A. Piserchio, and R. Ghose. (2022). Structural basis for the recognition of the bacterial tyrosine kinase Wzc by its cognate tyrosine phosphatase Wzb. Proc. Natl. Acad. Sci. USA 119: e2201800119. 35737836
Becker, A. and A. Pühler. (1998). Specific amino acid substitutions in the proline-rich motif of the Rhizobium meliloti ExoP protein result in enhanced production of low-molecular-weight succinoglycan at the expense of high-molecular-weight succinoglycan. J. Bacteriol. 180: 395-399. 9440529
Bianco, M.I., M. Jacobs, S.R. Salinas, A.G. Salvay, M.V. Ielmini, and L. Ielpi. (2014). Biophysical characterization of the outer membrane polysaccharide export protein and the polysaccharide co-polymerase protein from Xanthomonas campestris. Protein Expr Purif 101: 42-53. 24927643
Collins, R.F., K. Beis, B.R. Clarke, R.C. Ford, M. Hulley, J.H. Naismith, and C. Whitfield. (2006). Periplasmic protein-protein contacts in the inner membrane protein Wzc form a tetrameric complex required for the assembly of Escherichia coli group 1 capsules. J. Biol. Chem. 281: 2144-2150. 16172129
Drummelsmith, J. and C. Whitfield. (2000). Translocation of group 1 capsular polysaccharide to the surface of Escherichia coli requires a multimeric complex in the outer membrane. EMBO J. 19: 57-66. 10619844
Hagelueken, G., H. Huang, I.L. Mainprize, C. Whitfield, and J.H. Naismith. (2009). Crystal structures of Wzb of Escherichia coli and CpsB of Streptococcus pneumoniae, representatives of two families of tyrosine phosphatases that regulate capsule assembly. J. Mol. Biol. 392: 678-688. 19616007
Huang, J. and M. Schell. (1995). Molecular characterization of the eps gene cluster of Pseudomonas solanacearum and its transcriptional regulation at a single promoter. Mol. Microbiol. 16: 977-989. 7476194
Mijakovic, I., S. Poncet, G. Boël, A. Mazé, S. Gillet, E. Jamet, P. Decottignies, C. Grangeasse, P. Doublet, P. Le Maréchal, and J. Deutscher. (2003). Transmembrane modulator-dependent bacterial tyrosine kinase activates UDP-glucose dehydrogenases. EMBO J. 22: 4709-4718. 12970183
Minic, Z., C. Marie, C. Delorme, J.M. Faurie, G. Mercier, D. Ehrlich, and P. Renault. (2007). Control of EpsE, the phosphoglycosyltransferase initiating exopolysaccharide synthesis in Streptococcus thermophilus, by EpsD tyrosine kinase. J. Bacteriol. 189:1351-1357. 16980450
Morona, J.K., J.C. Paton, D.C. Miller, and R. Morona. (2000). Tyrosine phosphorylation of CpsD negatively regulates capsular polysaccharide biosynthesis in Streptococcus pneumoniae. Mol. Microbiol. 35: 1431-1442. 10760144
Morona, J.K., R. Morona, D.C. Miller, and J.C. Paton. (2002). Streptococcus pneumonia capsule biosynthesis protein CpsB is a novel manganese-dependent phosphotyrosine-protein phosphatase. J. Bacteriol. 184: 577-583. 11751838
Morona, J.K., R. Morona, D.C. Miller, and J.C. Paton. (2003). Mutational analysis of the carboxy-terminal (YGX)4 repeat domain of CpsD, an autophosphorylating tyrosine kinase required for capsule biosynthesis in Streptococcus pneumoniae. J. Bacteriol. 185: 3009-3019. 12730159
Nadler, C., S. Koby, A. Peleg, A.C. Johnson, K.C. Suddala, K. Sathiyamoorthy, B.E. Smith, M.A. Saper, and I. Rosenshine. (2012). Cycling of Etk and Etp phosphorylation states is involved in formation of group 4 capsule by Escherichia coli. PLoS One 7: e37984. 22675501
Niemeyer, D. and A. Becker. (2001). The molecular weight distribution of succinoglycan produced by Sinorhizobium meliloti is influenced by specific tyrosine phosphorylation and ATPase activity of the cytoplasmic domain of the ExoP protein. J. Bacteriol. 183: 5163-5170. 11489870
Paulsen, I.T., A.M. Beness, and M.H. Saier, Jr. (1997). Computer-based analyses of the protein constituents of transport systems catalyzing export of complex carbohydrates in bacteria. Microbiology 143: 2685-2699. 9274022
Peleg, A., Y. Shifrin, O. Ilan, C. Nadler-Yona, S. Nov, S. Koby, K. Baruch, S. Altuvia, M. Elgrably-Weiss, C.M. Abe, S. Knutton, M.A. Saper, and I. Rosenshine. (2005). Identification of an Escherichia coli operon required for formation of the O-antigen capsule. J. Bacteriol. 187: 5259-5266. 16030220
Shrivastava, A., R.G. Rhodes, S. Pochiraju, D. Nakane, and M.J. McBride. (2012). Flavobacterium johnsoniae RemA is a mobile cell surface lectin involved in gliding. J. Bacteriol. 194: 3678-3688. 22582276
Temel DB., Dutta K., Alphonse S., Nourikyan J., Grangeasse C. and Ghose R. (2013). Regulatory interactions between a bacterial tyrosine kinase and its cognate phosphatase. J Biol Chem. 288(21):15212-28. 23543749
Vincent, C., B. Duclos, C. Grangeasse, E. Vaganay, M. Riberty, A.J. Cozzone, and P. Doublet. (2000). Relationship between exopolysaccharide production and protein-tyrosine phosphorylation in Gram-negative bacteria. J. Mol. Biol. 304: 311-321. 11090276
Vincent, C., P. Doublet, C. Grangeasse, E. Vaganay, A.J. Cozzone, and B. Duclos. (1999). Cells of Escherichia coli contain a protein-tyrosine kinase, Wzc, and a phosphotyrosine-protein phosphatase, Wzb. J. Bacteriol. 181: 3472-3477. 10348860
Whitfield, C. (2006). Biosynthesis and assembly of capsular polysaccharides in Escherichia coli. Annu. Rev. Biochem. 75: 39-68. 16756484
Whitfield, C. and I.S. Roberts. (1999). Structure, assembly and regulation of expression of capsules in Escherichia coli. Mol. Microbiol. 31: 1307-1319. 10200953