Bacterial surface proteins

Kim SH, Shin DS, Oh MN, Chung SC, Lee JS, Oh KB. Inhibition of the bacterial surface protein anchoring transpeptidase sortase by isoquinoline alkaloids. Biosci Biotechnol Biochem 2004 68 421-424. 

Dean, P., and Kenny, B. (2004). Intestinal barrier dysfunction by enteropathogenic Escherichia coli is mediated by two effector molecules and a bacterial surface protein. Mol. Microbiol. 54, 665-675. 

First, bacterial adhesion (usually gram-positive cocci and filamentous bacteria) occurs primarily through a Ca + complex formation between carboxyl (COO ) and phosphate (HPOs ) groups of bacterial surface and acquired pelhcle, although van der Waals forces and repulsive electrostatic forces are also present. Some specific bacterial surface proteins also serve as adhesins for specific receptors on acquired peUicle. Pellicle-integrated immunoglobulins also bind bacteria specifically. 

Insertion of particular peptide motifs into proteins is not only a common method for protein analysis and purification but also for the development of new biotechnobgjes. Engineered proteins with controlled binding to other molecules include e.g., short metal-binding peptides in bacterial surface proteins for bioaccumulation and bioremediation purposes " or epitope-ta ed emgmies as a molecular sensor system, whose activity is modulated by anti-epitope antibodies."... 

The thermodynamic model is, like the DLVO theory, only applicable for the adhesion in vitro. Both models are based upon non-specific interactions occurring between particles (cells) and solid surfaces. In vivOr or under in vivo like conditions, specific interactions also have to be taken into account. Such specific interactions have been shown to mediate adhesion between bacteria and natural substrata, such as adhesion of streptococci to dental enamel,29 y adhesion of E. coli to uroepithelial cells.30 Although not clearly demonstrated for the bacterial adhesion to synthetic polymers, it is highly possible that specific interactions, e.g. between bacterial surface proteins and protein layers adsorbed on the polymer surface, play an important role as well. 

UB Sleytr, P Messner, D Pum, M Sara, eds. Crystalline Bacterial Cell Surface Proteins. Austin, TX Landes/Academic, 1996. 

Although ribosomal proteins are readily observed as in Figures 13.7 and 13.8 altered matrix conditions can alter the relative ionization of bacterial whole-cell compounds. A systematic analysis involving laser power/fluence and sample preparation conditions reveals that if the concentrated trifluo-roacetic acid is added and the laser power increased above optimal conditions, ionization of bacterial surface compounds can be enhanced. Figure 13.9 is the resulting 9.4 T MALDI-FTMS, seen are both the Braun s lipoprotein56,57 and the Murein lipoprotein. Both of these compounds are complex combinations of hydrocarbon lipids attached to a protein base. This is the first MALDI-FTMS observation of surface proteins desorbed directly from whole cells by influencing ionization conditions. 

More recently, increasing research attention has focused upon the use of mucoadhe-sive delivery systems in which the biopharmaceutical is formulated with/encapsulated in molecules that interact with the intestinal mucosa membranes. The strategy is obviously to retain the drug at the absorbing surface for a prolonged period. Non-specific (charge-based) interactions can be achieved by the use of polyacrylic acid, whereas more biospecihc interactions are achieved by using selected lectins or bacterial adhesion proteins. Despite intensive efforts, however, the successful delivery of biopharmaceuticals via the oral route remains some way off. 

The precise function of many acute-phase proteins is not known. C-reactive protein binds lipids, whilst a-macroglobulin and ceruloplasmin can scavenge some reactive oxygen metabolites. However, many acute-phase proteins are glycoproteins and can bind to bacterial surfaces hence, they may serve as non-specific opsonins for phagocytosis, and their synthesis is stimulated by IL-1 and IL-6. 

The precise chemical interactions between an adhesin and its receptor are also important. For example, direct- and water-mediated hydrogen bonds are the most important interactions within the carbohydrate-recognition domain in carbohydrate-binding adhesins on the host cell surface (Weis and Drickamer, 1996). Nonpolar van der Waals interactions and hydrophobic "stacking of the receptor oligosaccharide rings with aromatic amino acid side chains of the bacterial adhesin protein also contribute to oligosaccharide-protein interactions. X-ray structural... 

Hydrophobin-protein interactions include those bacterial surface components that promote adhesion to host cell surfaces via hydrophobic moieties that are often thought to be nonspecific (Rosenberg and Doyle, 1990 Rosenberg and Kjelleberg, 1986 Rosenberg et al, 1996). 

The initial adherence of pathogens to host cell surfaces is considered an essential step in colonization and infection (Savage, 1977, 1984). Therefore, identifying the bacterial molecules that mediate adherence has been a major area of research, especially since these molecules may serve as targets for anfi-adherence strategies. As discussed previously (Section VI), the detailed interactions between a pathogen and a host cell are often mediated by proteinaceous surface structures on the bacterial surface. These bacterial proteins are referred to as adhesins (Finlay and Falkow, 1989), and are most often foimd on the tips of bacterial fimbriae or pili (fimbrial adhesins), but may also be anchored in the bacterial membrane so that it can be presented on the bacterial outer membrane (afimbrial adhesins) (Sharon and Ofek, 1986). Models of fimbrial and afimbrial adhesins of some human pathogens are discussed here. 

Striking is the resemblance between our model structure and the multi-stranded -barrels known for various membrane proteins [42] and poreforming toxins [43]. The formation of an aqueous pore in the lipid bilayer would indeed offer an explanation for the observed bilayer conductivity induced by gramicidin S upon membrane binding [6]. The peptidedipid ratio of 1 40 at which this structure could be trapped for NMR analysis appears to be biologically relevant, as the minimum inhibitory concentration of gramicidin S corresponds to far more than an equimolar ratio of peptides per lipid molecule on the bacterial surface [34,35]. 

Summary. We recently developed an all-atom free energy force field (PFFOl) for protein structure prediction with stochastic optimization methods. We demonstrated that PFFOl correctly predicts the native conformation of several proteins as the global optimum of the free energy surface. Here we review recent folding studies, which permitted the reproducible all-atom folding of the 20 amino-acid trp-cage protein, the 40-amino acid three-helix HIV accessory protein and the sixty amino acid bacterial ribosomal protein L20 with a variety of stochastic optimization methods. These results demonstrate that all-atom protein folding can be achieved with present day computational resources for proteins of moderate size. 

---