Hormone—receptor complex formation

FIGURE 15.21 Hormone (H) binding to its receptor (R) creates a hormone receptor complex (H R) that catalyzes GDP-GTP exchange on the o -subunit of the heterotrimer G protein (G ), replacing GDP with GTP. The G -subunit with GTP bound dissociates from the /37-subunits and binds to adenylyl cyclase (AC). AC becomes active upon association with G GTP and catalyzes the formation of cAMP from ATP. With time, the intrinsic GTPase activity of the G -subunit hydrolyzes the bound GTP, forming GDP this leads to dissociation of G GDP from AC, reassociation of G with the /Sy subunits, and cessation of AC activity. AC and the hormone receptor H are integral plasma membrane proteins G and G are membrane-anchored proteins. 

The action of adrenaline (or noradrenaline) involves binding to an extracellular receptor, of which there are two classes, the a- and p-receptor. When the hormone binds to the P-receptor, the hormone-receptor complex activates adenyl cyclase, which catalyses the formation of cyclic AMP from ATP. 

Factors that affect the formation of the hormone-receptor complex. 

Fig. 1. Grouping of hematopoietic cytokine receptors by shared receptor usage. The majority of the hematopoietic cytokine receptors incorporate one of three shared signaling receptors, either the common beta (/ c) chain, the common gamma (7,-) chain or gplSO. The crystal structure of the growth hormone (red) complex (inset) was the first structure of a four helix bundle cytokine in complex with its receptor (green) (de Vos et al, 1992) and established the paradigm of cytokine/receptor complex formation. (See Color Insert.)...

Fondell JD, Roy AL, Roeder RG. 1993. Unliganded thyroid hormone receptor inhibits formation of a functional preinitiation complex implications for active repression. Genes Dev. 7 1400-10... 

Several studies have highlighted the importance of multidomain FKBPs in the control of signal transduction pathways. For example, hFKBP51 and hFKBP52 have been found in steroid hormone receptor complexes and are thought to play an important role in complex formation and translocation of receptor-ligand complexes from the cytosol into the nucleus [82,83], Notably, these multidomain FKBPs share structural characteristics as demonstrated by an N-terminal PPIase... 

Figure 14.10 Diagrammatic representation of regulation of the opening of an ion channel by phosphoiylation of a protein in the channel. The neurotransmitter-receptor complex functions as a nucleotide exchange factor to activate a G-protein which then activates a protein kinase. This is identical to control of G-proteins in the action of hormones (Chapter 12, see Figure 12.21). Phosphorylation of a protein in the ion channel opens it to allow movement of Na+ ions. The formation of the complex, activation of the G-protein and the kinase takes place on the postsynaptic membrane. An example of the structural organisation and the involvement of a G-protein is shown in Chapter 12 (Figure 12.6).

Fig. 4.8. Functional domains, DNA-binding and HRE structure of the steroid hormone receptors. a) domain structure of the steroid hormone receptor. AFl, AF2 domains that mediate the stimulation of the transcription, b) schematic representation of the two Zn -Cys4 binding motils of the DNA-binding domains, c) Complex formation between the dimeric DNA-binding domains of the gluccocorticoid receptor and the HRE. The black spheres represent Zn ions. After Luisi et al., 199L d) Consensus sequence and configuration of the HRE elements of the steroid hormone receptor.

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