This family consists of several eukaryotic corticotropin-releasing factor binding proteins (CRF-BP or CRH-BP). Corticotropin-releasing hormone (CRH) plays multiple roles in vertebrate species. In mammals, it is the major hypothalamic releasing factor for pituitary adrenocorticotropin secretion, and is a neurotransmitter or neuromodulator at other sites in the central nervous system. In non-mammalian vertebrates, CRH not only acts as a neurotransmitter and hypophysiotropin, it also acts as a potent thyrotropin-releasing factor, allowing CRH to regulate both the adrenal and thyroid axes, especially in development. CRH-BP is thought to play an inhibitory role in which it binds CRH and other CRH-like ligands and prevents the activation of CRH receptors. There is however evidence that CRH-BP may also exhibit diverse extra and intracellular roles in a cell specific fashion and at specific times in development [].
This is the immunoglobulin-like domain (IGD) found in leptin receptors (LEP-R), also known as obesity receptors (ObR). ObR is a single membrane-spanning receptor belonging to the class I cytokine receptor family. All isoforms have an identical extracellular part consisting of six domains: an N-terminal domain (NTD), two CRH domains (CRH1 and CRH2), an immunoglobulin-like domain (IGD), and two additional membrane-proximal fibronectin type III (FN III) domains. ObR activation depends on the CRH2, IGD, and FN III domains, however the CRH2 domain is the major leptin-binding determinant in the receptor. The IGD and membrane-proximal domains have no detectable affinity for the ligand, but are nonetheless indispensable for receptor activation. Deletion of the IGD results in a receptor with wild-type affinity for leptin, but completely devoid of biological activity [, ].
This entry represents a structural domain found in both the histidine-containing phosphocarrier protein HPr, as well as its structural homologues, which includes the catabolite repression protein Crh found in Bacillus subtilis [, ]. This domain has a alpha+beta structure found in two layers with an overall architecture of an open faced β-sandwich in which a β-sheet is packed against three α-helices. The histidine-containing phosphocarrier protein (HPr) is a central component of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS), which transfers metabolic carbohydrates across the cell membrane in many bacterial species [, ]. PTS catalyses the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is as follows: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to Enzyme I (EI) of the PTS, which in turn transfers it to the phosphoryl carrier protein (HPr) [, ]. Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease complex (enzymes EII/EIII). HPr [, ]is a small cytoplasmic protein of 70 to 90 amino acid residues. In some bacteria, HPr is a domain in a larger protein that includes a EIII(Fru) (IIA) domain and in some cases also the EI domain. A conserved histidine in the N-terminal section of HPr serves as an acceptor for the phosphoryl group of EI. In the central part of HPr, there is a conserved serine which (in Gram-positive bacteria only) is phosphorylated by an ATP-dependent protein kinase; a process which probably play a regulatory role in sugar transport. Regulatory phosphorylation at the conserved Ser residue does not appear to induce large structural changes to the HPr domain, in particular in the region of the active site [, ].
This entry represents a structural domain found in both the histidine-containing phosphocarrier protein HPr, as well as its structural homologues, which includes the catabolite repression protein Crh found in Bacillus subtilis [, ]. This domain has a alpha+beta structure found in two layers with an overall architecture of an open faced β-sandwich in which a β-sheet is packed against three α-helices. The histidine-containing phosphocarrier protein (HPr) is a central component of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS), which transfers metabolic carbohydrates across the cell membrane in many bacterial species [, ]. PTS catalyses the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is as follows: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to Enzyme I (EI) of the PTS, which in turn transfers it to the phosphoryl carrier protein (HPr) [, ]. Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease complex (enzymes EII/EIII). HPr [, ]is a small cytoplasmic protein of 70 to 90 amino acid residues. In some bacteria, HPr is a domain in a larger protein that includes a EIII(Fru) (IIA) domain and in some cases also the EI domain. A conserved histidine in the N-terminal section of HPr serves as an acceptor for the phosphoryl group of EI. In the central part of HPr, there is a conserved serine which (in Gram-positive bacteria only) is phosphorylated by an ATP-dependent protein kinase; a process which probably play a regulatory role in sugar transport. Regulatory phosphorylation at the conserved Ser residue does not appear to induce large structural changes to the HPr domain, in particular in the region of the active site [, ].
