ABC transporter MsbA

Fig. 1.2 Export of LPS and its precursors in E. coli. O-antigen oligosaccharides is assembled separately on undecaprenyl diphosphate, flipped from the cytoplasmic face to the periplasmic face of the inner membrane by the transporter Wzx, and polymerized on the periplasmic face of the inner membrane by Wzy and Wzz. The ABC transporter MsbA flips the core-lipid A from the inner surface to the outer surface of the inner membrane. Then the polymerized O-antigen is transferred to the core-lipid A in the periplasm by WaaL. The protein LptA, LptB, LptC, LptF and LptG might shuttle the nascent LPS from the periplasmic face of the inner membrane to the inner layer of the outer membrane. The outer membrane proteins LptD and LptE are required for the assembly of LPS into the outer surface of the outer membrane (Ma et al., 2008 Wu et al., 2006)...

Ward, A., Reyes, C.L., Yu, J., Roth, C.B., Chang, G. Flexibility in the ABC transporter MsbA alternating access with a twist. Proc Natl Acad Sci USA 104 (2007) 19005-19010. 

Keyes, C. L., and Ciiang, G, 2005. Structure of the ABC transporter MsbA in complex with A DP. vanadate and I ipopoly saccharide. Samce 308 1028 31. 

Zou P, Mchaourab HS (2009) Alternating access of the putative substrate-binding chamber in the ABC transporter MsbA. J Mol Biol 393(3) 574—585... 

Chang, G., Roth, C. B., Structure of MsbA from E. coli a homolog of the multidrug resistance ATP binding cassette (ABC) transporters, Science 2001, 293, 1793-1800. 

Chang, G. Structure of MsbA from Vibrio cholerae. a multidrug resistance ABC transporter homolog in a closed conformation. /. Mol. Biol. 330 419-430, 2003. 

FIGURE 11-41 Structures of two ABC transporters of E, coli, (a) The lipid A flippase MsbA (PDB ID 1JSQ) and (b) the vitamin B12 importer BtuCD (PDB ID 1L7V). Both structures are homodimers. The two nucleotidebinding domains (NBDs, in red) extend into the cytoplasm. In (b), residues involved in ATP binding and hydrolysis are shown as ball-and-stick structures. Each monomer of MsbA has six transmembrane helical segments (blue), and each monomer of BtuCD has ten. 

The structure of P-glycoprotein has not been determined. However, X-ray crystallographic structures have been determined for bacterial members of the ABC transporter family the MsbA lipid A "flippases" from E. coli (72) and Vibrio cholera (73) and the cobal-amin uptake transporter BtuCD protein of E. coli (74). These structures are consistent with the overall picture of P-glycoprotein function described here. 

Reyes CL, Ward A, Yu J, Chang G (2006) The stmctures of MsbA insight into ABC transporter-mediated multidrug efflux. FEBS Lett 580(4) 1042-1048... 

Chang, G. (2003). Structure of MsbA from Vibrio cholera a multidrug resistance ABC transporter homolog in a closed conformation. / Mol Biol, Vol.330, No.2, pp. 419-30 Chang, G. Roth, C.B. (2001). Structure of MsbA from E. coli a homolog of the multidrug resistance ATP binding cassette (ABC) transporters. Science, Vol.293, No.5536, p>p. 1793-800... 

Seeger, M.A. van Veen, H.W. (2009). Molecular basis of multidrug transport by ABC transporters. Biochim BiophysActa, Vol.1794, No.5, pp. 725-2>7 Seigneuret, M. Garnier-Suillerot, A. (2003). A structural model for the open conformation of the mdrl P-glycoprotein based on the MsbA crystal structure. / Biol Chem, Vol.278, No.32, pp. 30115-24... 

MsbA is a homodimer of a polypeptide consisting of fused nucleotide binding domains (NBDs) and TMDs, a common feature of bacterial ABC exporters. The substrate is picked up from the inner leaflet of the membrane, and exported to the outside of the membrane by a conformational change of the transporter. Crystal structures of MsbA exist in the apo inward-facing conformation (PDB 3B5W, Ca atoms only) and in the AMPPNP-bound outward-facing conformation (PDB 3B60,... 

The hpad flipp>ase MsbA is an ABC pa-otein that is responsible for the transport for lipid A and hpopolysaccharide (LPS). A non-functional MsbA leads to accumulation of lipopolysaccharide and phospholipids in the inner membrane of gram-negative bacteria... 

Zhou, Z., White, K. A., Polissi, A., Georgopoulos, C., and Raetz, C. R. H. (1998). Function of the Escherichia coli msbA gene, an essential ABC family transporter, in lipid A and phospholipid biosynthesis. J. Biol. Chem 273, 12466 -12475. 

Polissi, A., and Georgopoulos, C. (1996). Mutational analysis and properties of the msbA gene of Escherichia coli, coding for an essential ABC family transporter. Mol. Microbiol. 20,1221-1233. 

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