Pertussis Structure

Bacterial lipid A structures typically act as TLR2 agonists however, there are some cases where such compounds act as antagonists (e.g., Bordetella pertussis lipid A, 9), which antagonize the TLR2-TLR6 heterodimer [37]. 

Fig. 14. Structural prediction and modeling of a fragment of FHA from B. pertussis containing Rl-repeats. (A) Successive stages in the modeling. From top to bottom identification of the consensus sequence repeat, generation of 2D template of the coil, and the modeled 3D structure. In the consensus sequence, letters indicate residues that are conserved at the level of >60% identity, x is any residue and filled circles represent bulky nonpolar residues. Apolar residues are in red glycine in green. In the 2D template, open circles denote any (but mainly polar) residues, while filled circles denote conserved, mainly nonpolar, residues. Circles inside the coil contour indicate side chains located inside the structure and circles outside the contour denote side chains facing the solvent. Arrows indicate /(-strands. (B) A fragment of the crystal structure of FHA (Clantin et al, 2004) (on the top, in green color) and the 3D model (bottom, in brown).

GM-CSF and IL-3 have been shown to compete for receptors in some types of cells (e.g. eosinophils and KG-1 cells), indicating some structural homology between GM-CSF and IL-3 receptors, perhaps because they share certain subunits or adapter proteins. GM-CSF occupancy results in phosphorylation of certain proteins, and because the receptor possesses no inherent kinase activity, receptor occupancy must be linked to kinase activity via the generation of second messenger molecules. Pretreatment of cells with pertussis toxin abolishes the effects of GM-CSF, indicating the involvement of G-proteins in signal transduction. Priming of neutrophil functions with GM-CSF involves the activation of phospholipases A2 and D. 

All of these experimental approaches have been adopted in neutrophil studies to show that activation of several receptor-mediated functions occurs via the participation of heterotrimeric G-proteins. In many cases, the conventional Gai/Gas nomenclature is used to describe these G-proteins, even though the subunits may not be linked to either inhibition or activation of adenylate cyclase. The nomenclature used is based on structural and functional similarities to other Ga-subunits in other cell types, and also on their sensitivities to cholera and pertussis toxins. Several of these G-proteins... 

Bordetella pertussis endotoxin, and with the ultimate hope of correlating structure and biological, in particular immunological, properties of lipopolysaccharides that compose this endotoxin. 

The necessity of establishing the presence of a structural element present in many endotoxins may be questioned, but it should be remembered that B.pertussis is a rather singular microorganism in every respect (6) whose classification itself is uncertain, and it has been observed by MacLennan, who first isolated this endotoxin (7), that the lethal toxicity of this material was considerably lower than that of enterobacterial endotoxins, an observation confirmed by both Kasai (8) and Nakase ( ). 

It was, therefore, considered imperative not to extrapolate results obtained with endotoxins of other bacteria, but to establish each structural feature of the pertussis endotoxin independently. 

The first identified cannabinoid receptor subtype, CB was cloned and demonstrated to have an amino acid sequence consistent with a tertiary structure typical of the seven transmembrane-spanning proteins that are coupled to G proteins. In addition to being found in the central nervous system, mRNA for CB has also been identified in testes. The central nervous system responses to cannabinoid compounds are believed to be mediated exclusively by CB, inasmuch as CB2 transcripts could not be found in brain tissue by either Northern analysis or in situ hybridization studies. CBj transduces signals in response to central-nervous-system-active constituents of C. sativa as well as synthetic bicyclic and tricyclic cannabinoid analogs, aminoalkylindole, and eicosanoid cannabimimetic compounds. CB is coupled to G, to inhibit adenylate cyclase activity and to a pertussis-sensitive G protein to regulate Ca2+ currents. 

H. Paulsen Synthesis of amino- and branched chain mono- and oligosaccharides L. Szabo Structural features and biological activity of the Bordella pertussis endotoxin... 

Burns DL. Subunit structure and enzymic activity of pertussis toxin. Microbiol. Sci. 1988 5 285-287. 

Based on the functional similarities between the pertussis toxin and the selectins (including their ability to bind to similar sialic acid-containing oligosaccharides structures), Rozdzinski et al. [166] and Heerze et al. [169] synthesized peptides from the regions of sequence similarity in an effort to find molecules that adhere to sialic acid-containing glycoconjugates. The recombinant subunits S2 and S3 of pertussis toxin and the synthetic peptides competitively inhibited adherence of neutrophils to selectin-coated surfaces and to endothelial cells in vitro. 

There is another large class of receptors whose occupancy by an agonisf leads to inhibition of adenylate cyclase. These include the tt2 adrenergic receptors, receptors for acetylcholine, adenosine, prostaglandin E2 (Chapter 21), somatostatin, and some receptors for dopamine. Their responses are mediafed by inhibitory proteins Gj, which closely resemble Gg in their sizes, amino acid sequences, and heterotrimeric structures, but which inhibit adenylate cyclase when activated. A clear distinction between the Gg and Gj proteins is evident in the fact that Gg is irreversibly activated by the action of cholera toxin, while G loses its ability to respond to occupied receptors when modified by the action of Pertussis toxin (Box 11-A). A specialized heterotrimeric G protein known as transducin mediates the light-induced activation of a cyclic GMP phosphodiesterase in the retina " (see Chapter 23). Its a subunit is designated aj. The related gustducin is found in taste buds. ... 

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