Bacterial toxin effector-membrane targeting: outside in, then back again - PubMed (original) (raw)
Review
Bacterial toxin effector-membrane targeting: outside in, then back again
Brett Geissler. Front Cell Infect Microbiol. 2012.
Abstract
Pathogenic bacteria utilize multiple approaches to establish infection and mediate their toxicity to eukaryotic cells. Dedicated protein machines deposit toxic effectors directly inside the host, whereas secreted toxins must enter cells independently of other bacterial components. Regardless of how they reach the cytosol, these bacterial proteins must accurately identify their intracellular target before they can manipulate the host cell to benefit their associated bacteria. Within eukaryotic cells, post-translational modifications and individual targeting motifs spatially regulate endogenous host proteins. This review focuses on the strategies employed by bacterial effectors to associate with a frequently targeted location within eukaryotic cells, the plasma membrane.
Keywords: bacterial effectors; intracellular targeting; plasma membrane; toxins.
Figures
Figure 1
Schematic summary of the toxic bacterial effectors that target host cell plasma membranes. Shown are three central pathways (T3SS, T4SS, MARTX) responsible for effector translocation into the host cell and the intracellular locations of the effectors with lipidation motifs (jagged lines at either end of an effector) or dedicated membrane localization domains (triangles, T3SS; squares, T4SS; circles, MARTX). Potential hydrophobic interactions with the membrane are indicated as yellow patches on the effector. CC, coiled-coil domain; UB, ubiquitination site; SCV, _Salmonella_-containing vacuole; LCV, _Legionella_-containing vacuole. See text for details.
Figure 2
Plasma membrane targeting motifs are not restricted to specific locations within the various effectors. The dedicated membrane localization domains (MLD) that have been identified are found at both termini and in the interior of their effectors. Many of these MLDs contain stretches of Ile/Leu/Val residues (yellow) to mediate hydrophobic membrane associations. In addition, regions rich in basic residues (dark blue) can enhance membrane binding by generating electrostatic interactions or serving as sites for host cell ubiquitination. Sites for host cell lipidation (red) are also found at both termini as well as on the interior of certain effectors, which is exposed following cysteine protease cleavage. Several prenylated effectors contain motifs that provide additional targeting information (gray) to identify specific locations within the PM.
Figure 3
Despite the shared overall structure for membrane associations by the four helical bundle membrane localization domains, their primary amino acid sequences show significant diversity. (A) Pairwise sequence alignment of all 24 of the currently identified 4HBMs organized according to their sequence identity. A schematic representation of the structure of the domains is depicted below alignment. To highlight their locations on either loops or helices, only basic (blue), hydrophobic (yellow), and Phe (magenta) residues are boxed. (B) Neighbor joining tree illustrating the phylogenetic relationships of the 4HBMs; tree is based on sequence pairwise identity. (C) Structural alignment of five different crystallized and modeled 4HBMs shows nearly complete overlap for all of the homologs, regardless of their primary amino acid sequence or associated catalytic domain.
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