Hormone-binding domain

Figure 13.19 Ribbon diagram of the stmcture of the extracellular domain of the human growth hormone. The hormone-binding region is formed by loops (yellow) at the hinge region between two fibronectin type III domains. (Adapted from J. Wells et al., Annu. Rev.

These receptors are unlike the well-characterised rhodopsin-like family in that they have a large extracellular N-terminus and hormone binding seems to be dominated by this domain rather than the transmembrane domains. Receptors in this class include... 

ACTIVATION OF TRANSCRIPTION by soluble hormones. The hormone is carried to its site of action by a carrier protein in the blood. The hormone crosses the membrane (by itself) and binds to a soluble receptor. A conformation change induced by hormone binding causes the receptor to expose its DNA binding site. This site binds to a specific sequence in the DNA upstream of genes that are to be activated for transcription. The transcription activation occurs through another domain of the protein that binds to components of the RNA polymerase complex. 

The initial step after cellular uptake of T4 is metabolic transformation to 3,5,3, -tri-iodothyronine (T3) (Fig. 52-8), which interacts with cytosolic and nuclear receptors, as well as with synaptosomal membrane binding sites of unknown function [25], Cytosolic receptors are proteins of 70 kDa that do not appear to undergo translocation to cell nuclei, nor do they appear to be nuclear proteins that have leaked out of cell nuclei during cell rupture nuclear receptors are proteins of 50 70 kDa that have both DNA-and hormone-binding domains [25,26,28],... 

ERs have domains responsible for nuclear location, hormone binding, dimerization, DNA binding, and transcription activation (Figs. 1.2 and 1.3) (Beato et al. 1996 Beato 1989 Fawell et al. 1990 Hall et al. 1999 Kumar et al. 1987). 

The LBD harbors a zone of interaction with hsp90. When the hormone binds with the corresponding domain in the receptor, the protein changes its conformation, losing its affinity for hsp90. As a result, the receptor loses its affinity for hsp90. 

Some signal pathways that activate the adenylate cyclase phosphorylate tyrosine residues (Y535) of the TAF2 domain, which, as previously mentioned, is dependent on hormone binding. In this case, modulation of the transcription... 

Parathyroid hormone (PTH) regulates calcium levels in blood and bone remodeling. The activation domain of that 84-amino acid polypeptide locates around the N-terminal (1-34 amino acids). Parathyroid hormone receptor is a typical G-protein coupled receptor, which is coupled to both adenyl cyclase/cAMP and PLCy/IP3/cytosolic Ca2+ intracellular signaling pathways. In order to identify the structural elements involved in the peptide hormone binding and signal initiation, Chorev et al. employed a photoaffinity scanning approach. The N-terminal amino acids were successively deleted or modified and the new N-terminus was replaced for photoreactive Bpa. The most active peptide ana-... 

This class of receptors transmits signals carried by hormones and growth factors. The structure consists of an extracellular domain for binding ligands and a cytoplasmic enzyme domain. The function of kinases is to enable phosphorylation. Phosphorylation regulates most aspects of cell life. 

Hurley DM, Accili D, Stratakis CA, et al. (1991) Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in famUial glucocorticoid resistance. J Clin Invest. 87, 680-686. 

The receptors for lipophilic signaling substances all belong to one protein superfamily. They are constructed in a modular fashion from domains with various lengths and functions. Starting from the N terminal, these are the regulatory domain, the DNA-binding domain, a nuclear localization sequence (see p. 228), and the hormone-binding domain (see p. 73D). 

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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