G-protein selectivity

Using chimaeric receptors it has been shown that swapping the third intracellular loop between receptors also swaps their G-protein selectivity. The G-protein-binding... 

For all GPCRs compiled in SEVENS database, we are planning to create G-protein selectivity profiles according to information of various number of ligands (>several million). 

Heximer SP, Srinivasa SP, Bernstein LS et al (1999) G protein selectivity is a determinant of RGS2 function. J Biol Chem 274 34253-9... 

Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. In Nature (London) 340 680-685 Laugwitz KL, Spicher K, Schultz G et al. (1994) Identification of receptor-activated G proteins selective immunoprecipitation of photolabeled G-protein a subunits. In Methods Enzymol. 237 283-294 Meyer T, Hilz H (1986) Production of anti-(ADP-ribose) antibodies with the aid of a dinucleotide-pyrophosphatase-resistent hapten and their application for the detection of mono(ADP-ribosyl)ated polypeptides. In Ear. J. Biochem. 155 157-165... 

D., Vischer, H.F., Mattick, C., Leurs, R., and Smit, M.J. (2006) Chemokine-directed trafficking of receptor stimulus to different g proteins selective inducible and constitutive signaling by human herpesvirus 6-encoded chemokine receptor U51. Molecular Pharmacology, 69, 888-898. 

U. Hobohra, M. Scharf, R. Schneider and G. Sander, Selection of representative protein data sets. Protein Sci. 1 (1992), 409-417. 

Myristic acid may be linked via an amide bond to the a-amino group of the N-terminal glycine residue of selected proteins (Figure 9.18). The reaction is referred to as A -myristoylation and is catalyzed by myristoyl—CoAtprolein N-myris-toyltransferase, known simply as NMT. A -Myristoyl-anchored proteins include the catalytic subunit of cAMP-dependent protein kinase, the ppSff tyrosine kinase, the phosphatase known as calcineurin B, the a-subunit of G proteins (involved in GTP-dependent transmembrane signaling events), and the gag proteins of certain retroviruses, including the FHV-l virus that causes AIDS. 

The most probable mechanism for inverse agonism is the same one operable for positive agonism namely, selective receptor state affinity. However, unlike agonists that have a selectively higher affinity for the receptor active state (to induce G-protein activation and subsequent physiological response) inverse agonists have a selectively higher affinity for the inactive receptor state and thus uncouple already spontaneously coupled [RaG] species in the system. 

Wildoer, M., Fong, J., Jones, R. M., Lunzer, M. M., Sharma, S. K., Kostensis, E., Portoghese, P. S., and Whistler, J. L. (2005). A heterodimer-selective agonist shows in vivo relevance of G-protein coupled receptor dimmers. Proc Natl. Acad. Sci. USA 102 9050-9055. 

G-protein-coupled Receptor Selective Sex Steroid Receptor Modulators... 

Kir3.2 Weaver mouse. A mutant mouse with cer ebellar degeneration and motor dysfunction resulting from a serine for glycine substitution in the -GYG- sequence of the K selectivity filter of Kir3.2. G-protein activated K conductances are abolished in the cerebellar neurons, leading to Ca2+ overload and cell death. 

Of the several classes of receptors for endogenous chemical signals [3], two are used as postsynaptic receptors in synaptic transmission ligand-gated ion channels (LGICs) and G protein-coupled receptors (GPCRs Fig. 1). Due to the large number of transmitters and the existence of several receptor types for almost all, postsynaptic receptor activation is the most diversified step of synaptic transmission. Table 1 shows selected neurotransmitter receptors. 

Sensory receptors expressed in particular in taste receptor cells of the taste buds that sense the five basic tastes salt, sour, sweet, bitter and umami (glutamate taste). Sodium type ion channels sense salty taste whereas sour taste is transduced by potassium type ion channels. The underlying cause of sweet, bitter, and umami tastes is the selective activation of different groups of G protein coupled receptors that discriminate between sweet, bitter, and umami tasting molecules. 

Wallraff, E., Schleicher, M., Modersitzki. M Reiger, D., Isenberg, G., Gerish, G. (1986). Selection of Dictyostelium mutants defective in cytoskeletal protein Use of an antibody that binds to the ends of alpha-actinin rods. EMBO J. 5,61-67. 

Current analytical methods have difficulty detecting picogram levels of nucleic acids, particularly when high levels of other biopolymers (e.g., proteins) are present. The most widely used assay method employed by the pharmaceutical industry involves a nick translation DNA hybridization method (1). This assay offers high sensitivity and selectivity but has a number of drawbacks. 

Patterning of enzyme monolayers on a solid surface was carried out by photoactivation of immobilized monolayer of caged -biotin derivatives in selected areas. Specific oriented binding of enzyme-avidin conjugates could be readily made to the photoactivated zones [42]. Oriented immobilization of G-protein-coupled receptors on a solid surface was also made possible on a biotinylated surface by first immobilizing streptavidin, followed by the immobilization of biotinylated G-protein-coupled receptor [43]. 

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