Membrane permeases

Figure 11.1 Schematic representation of iron uptake mechanisms, (a) The transferrin-mediated pathway in animals involves receptor-mediated endocytosis of diferric transferrin (Tf), release of iron at the lower pH of the endocytic vesicle and recycling of apoTf. (b) The mechanism in H. influenzae involves extraction of iron from Tf at outer membrane receptors and transport to the inner membrane permease system by a periplasmic ferric binding protein (Fbp). From Baker, 1997. Reproduced by permission of Nature Publishing Group.

This hypothesis excludes lipophilic complexes [19,50] and complexes subject to accidental uptake via membrane permeases [51,52], for which the analysis would be basically different [5,18]. In this sense, we also disregard here any adsorption of M in the form of its complex ML. 

Likewise, for zinc, bacteria have developed active uptake systems (Hantke, 2001). In many bacteria the high-affinity Zn2+ uptake system uses an ABC transporter of the cluster 9 family, which mostly transports zinc and manganese and is found in nearly all bacterial species. First identified in cyanobacteria and pathogenic streptococci, but also found in E. coli, the system is encoded by three genes ZnuABC and consists of an outer membrane permease ZnuB, a periplasmic-binding protein ZnuA and a cytoplasmic ATPase ZnuC. Low-affinity transporters of the ZIP family, described later in this chapter, such as ZupT, have also been shown to be involved in bacterial zinc uptake. 

ABC pumps and membrane permeases involved in drug efflux have also been found in other Candida strains of clinical relevance. CdCDRl and CdCDP2 encode... 

El Bissati, K., Zufferey, R., Witola, W. H., Carter, N. S., Ullman, B., and Ben Mamoun, C. (2006). The plasma membrane permease PfNTl is essential for purine salvage in the human malaria parasite Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 103,9286-9291. 

For example, when tissues were deprived of sodium for several days the site density increased 3-fold from around 250//im, but more importantly there was a proportional increase in the level of transport which was maintained by the epithelium [197] (Figure 1.15). This effect seems an important homeostatic device possessed by the cell to deal with exposures to divergent sodium concentrations. Furthermore, the result indicates that the entry step, rather than the exit step from the epithelium which requires sodium pumping, is the rate determinant of the level of transport. The time course of the effect of sodium deprivation may mean that it is dependent on the de novo synthesis of new membrane permeases. However, increasing the membrane potential across the mucosal face of the cells causes an immediate appearance of new channels, while reducing the potential does the converse [198], indicating that there are binding sites (and... 

Essential solutes able to permeate the outer membrane are rapidly sequestered by the appropriate periplasmic binding protein. This lowers the effective free solute concentration facilitating further solute diffusion. The binding protein is capable of mediating the rapid transfer of the solute to the appropriate cytoplasmic membrane permease which transports the ligand to the cell interior. 

Nguyen, T.X., Yen, M.R., Barabote, R.D., and Saier, M.H., Jr. (2006) Topological predictions for integral membrane permeases of the phosphoenolpyruvate sugar phosphotransferase system. J Mol Microbiol Biotechnol 11, 345-360. 

Furthermore, if the antibiotic passes membranes through a specific port of entry, its mutational loss leads to resistance. The lack of the outer membrane protein OprD in P. aeruginosa causes resistance to the (3-lactam antibiotic imipenem. Fosfomycin passes the cytoplasmic membrane via an L-a-glycerol phosphate permease. This transport system is not essential for bacterial growth and therefore mutants with a reduced expression are frequently selected under therapy. 

Aligned sequences of 16 members of the sugar transporter family. Residues which are identical in 5=50% of the 16 sugar-transporter sequences (excluding the quinate transporter (qa-y), the citrate transporter (CIT), the tetracycline transporter (pBR322) and lac permease (LacY)) are highlighted, and recorded below the sequences as CONSERVED . The locations of predicted membrane-spanning helices are indicated by horizontal bars. The sequences were taken from the references cited in the text. 

The information obtained from the experiments described above can be used to construct models for the three-dimensional arrangement of the membrane-spanning helices within the transport proteins. One such model, which takes the diameter of an a-helix as 1.1 nm and seems to fit the measured dimensions of lac permease quite nicely, is illustrated in Fig. 5, although it must be emphasized that this is only one of... 

When the new term permease was coined to designate bacterial membrane proteins specialized in the transport of specific metabolites [1,2], it covered a concept which was not quite new. The existence of membrane transport systems had been demonstrated in animal tissues by Cori as early as 1925 (see [3]). However, the discovery and characterization of permeases in bacteria revolutionized prospects for studying the properties of transport systems, opening the way to a new field and a very fruitful methodology. 

In bacteria, accumulation of substrates against a concentration gradient can occur through two main classes of transport systems (see [30] for a summary). The prototype of the first class of transporters is the /3-galactoside permease of Escherichia coli (see [31]). It is a relatively simple system involving only a single membrane-bound protein. It catalyzes a lactose-H symport. Other transporters... 

Ovchinnikov 234 237) has shown that bovine rhodopsin, although quite different in amino acid sequence (348 residues), also forms seven transmembrane helices. This structural similarity between bacterial and mammalian light activated membrane proteins is remarkable. Since the two amino acid sequences have little in common it would appear that the necessary requirement is seven transmembrane helices to form a channel which is specific for proton migration. For example it has been suggested that a similar arrangement and function is performed by the lactose permease of E. coli237). 

Figure 4.4 Comparison of oxidase-dependent iron transport in mammals and yeast. In mammals, the plasma glycoprotein cerulpolasmin mediates iron oxidation, facilitating iron export from the cells and delivery to other tissues throughout the body. In yeast, Fet3p, an integral membrane protein mediates iron oxidation, resulting in plasma membrane iron transport through the permease Ftrlp. Reprinted from Askwith and Kaplan, 1998. Copyright (1998), with permission from Elsevier Science.

Jung, K., Voss, J., He, M., Hubbell, W. L., and Kaback, H. R. (1995) Engineering a metal binding site within a polytopic membrane protein, the lactose permease of Escherichia coli. Biochemistry 34, 6272-6277. 

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