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Signalling Factors (signalling + factor)
Selected AbstractsCarbohydrate-binding properties of goat secretory glycoprotein (SPG-40) and its functional implications: structures of the native glycoprotein and its four complexes with chitin-like oligosaccharidesACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2007Punit Kaur A 40,kDa glycoprotein (SPG-40) secreted during involution works as a protective signalling factor through its binding to viable cells. The crystal structure of the native protein has been determined at 2.3,Å resolution. This is the first report on the carbohydrate-binding properties of SPG-40; the structure determinations of the complexes of SPG-40 with four oligosaccharides of different lengths at resolutions ranging from 2.2 to 2.8,Å are described. Carbohydrate-binding studies with N -acetylglucosamines (GlcNAcn, n = 3,6) using fluorescence spectroscopy revealed poor binding effects with GlcNAc3 and GlcNAc4, while GlcNAc5 and GlcNAc6 bound to SPG-40 with considerable strength; the dissociation constants (Kd) were estimated to be 260 ± 3 and 18 ± 4,µM, respectively. SPG-40 was cocrystallized with GlcNAc3, GlcNAc4, GlcNAc5 and GlcNAc6. The overall structure of native SPG-40 was essentially similar to that reported previously at low resolution. The structures of its complexes with GlcNAc3, GlcNAc4, GlcNAc5 and GlcNAc6 revealed the positions of these oligosaccharides in the carbohydrate-binding groove and provided insights into the mechanism of binding of oligosaccharides to SPG-40, indicating that the preferred subsites in the carbohydrate-binding groove of SPG-40 were from ,4 to ,2. The structure of the protein remained unperturbed upon binding of GlcNAc3 and GlcNAc4, but the structure changed significantly upon binding of GlcNAc5 and GlcNAc6. Significant conformational variations were observed in the sugar-binding groove: Trp78 partially flipped out of the barrel in GlcNAc5, while in the GlcNAc6 complex a completely flipped-out Trp78 was observed along with several other conformational changes, including those of Asp186 and Arg242. Such changes upon binding to carbohydrates have not previously been observed in chitin-hydrolyzing chitinases and reflect less favourable binding of carbohydrates to SPG-40. As this appears to essentially be a binding protein, this loss of binding affinity might be compensated by other intermolecular interactions such as protein,protein interactions and also by the binding of its own glycan chain. [source] Structure of the buffalo secretory signalling glycoprotein at 2.8,Å resolutionACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 4 2007Abdul S. Ethayathulla The crystal structure of a 40,kDa signalling glycoprotein from buffalo (SPB-40) has been determined at 2.8,Å resolution. SPB-40 acts as a protective signalling factor by binding to viable cells during the early phase of involution, during which extensive tissue remodelling occurs. It was isolated from the dry secretions of Murrah buffalo. It was purified and crystallized using the hanging-drop vapour-diffusion method with 19% ethanol as the precipitant. The protein was also cloned and its complete nucleotide and amino-acid sequences were determined. When compared with the sequences of other members of the family, the sequence of SPB-40 revealed two very important mutations in the sugar-binding region, in which Tyr120 changed to Trp120 and Glu269 changed to Trp269. The structure showed a significant distortion in the shape of the sugar-binding groove. The water structure in the groove is also drastically altered. The folding of the protein chain in the flexible region comprising segments His188,His197, Phe202,Arg212 and Tyr244,Pro260 shows large variations when compared with other proteins of the family. [source] The mode of action of thiazolidinediones,DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S2 2002Hans Hauner Abstract The thiazolidinediones (TZDs) or ,glitazones' are a new class of oral antidiabetic drugs that improve metabolic control in patients with type 2 diabetes through the improvement of insulin sensitivity. TZDs exert their antidiabetic effects through a mechanism that involves activation of the gamma isoform of the peroxisome proliferator-activated receptor (PPAR,), a nuclear receptor. TZD-induced activation of PPAR, alters the transcription of several genes involved in glucose and lipid metabolism and energy balance, including those that code for lipoprotein lipase, fatty acid transporter protein, adipocyte fatty acid binding protein, fatty acyl-CoA synthase, malic enzyme, glucokinase and the GLUT4 glucose transporter. TZDs reduce insulin resistance in adipose tissue, muscle and the liver. However, PPAR, is predominantly expressed in adipose tissue. It is possible that the effect of TZDs on insulin resistance in muscle and liver is promoted via endocrine signalling from adipocytes. Potential signalling factors include free fatty acids (FFA) (well-known mediators of insulin resistance linked to obesity) or adipocyte-derived tumour necrosis factor-, (TNF-,), which is overexpressed in obesity and insulin resistance. Although there are still many unknowns about the mechanism of action of TZDs in type 2 diabetes, it is clear that these agents have the potential to benefit the full ,insulin resistance syndrome' associated with the disease. Therefore, TZDs may also have potential benefits on the secondary complications of type 2 diabetes, such as cardiovascular disease. Copyright © 2002 John Wiley & Sons, Ltd. [source] Chromatin regulation functions in plant abiotic stress responsesPLANT CELL & ENVIRONMENT, Issue 4 2010JONG-MYONG KIM ABSTRACT Plants respond and adapt to drought, cold and high-salinity stress in order to survive. Molecular and genomic studies have revealed that many stress-inducible genes with various functions and signalling factors, such as transcription factors, protein kinases and protein phosphatases, are involved in the stress responses. Recent studies have revealed the coordination of the gene expression and chromatin regulation in response to the environmental stresses. Several histone modifications are dramatically altered on the stress-responsive gene regions under drought stress conditions. Several chromatin-related proteins such as histone modification enzymes, linker histone H1 and components of chromatin remodeling complex influence the gene regulation in the stress responses. This review briefly describes chromatin regulation in response to drought, cold and high-salinity stress. [source] Structure of a bovine secretory signalling glycoprotein (SPC-40) at 2.1,Å resolutionACTA CRYSTALLOGRAPHICA SECTION D, Issue 9 2006Janesh Kumar A recently discovered new class of 40,kDa glycoproteins forms a major component of the secretory proteins in the dry secretions of non-lactating animals. These proteins are implicated as protective signalling factors that determine which cells are to survive during the processes of drastic tissue remodelling. In order to understand its role in the remodelling of mammary glands, the detailed three-dimensional structure of the bovine signalling glycoprotein (SPC-40) has been determined using X-ray crystallography. SPC-40 was purified from bovine dry secretions and crystallized using the hanging-drop vapour-diffusion method. The crystals belong to the orthorhombic space group P212121, with unit-cell parameters a = 62.6, b = 67.4, c = 106.9,Å. The protein was also cloned in order to determine its complete amino-acid sequence. Its three-dimensional structure has been determined using data to 2.1,Å resolution. The amino-acid sequence determination of SPC-40 reveals two potential N-glycosylation sites at Asn39 and Asn345, but electron density for a glycan chain was only present at Asn39. The protein adopts a conformation with the classical (,/,)8 -barrel fold of triosephosphate isomerase (TIM barrel; residues 1,237 and 310,360) with the insertion of a small ,+, domain (residues 240,307) similar to that observed in chitinases. However, the substitution of Leu for Glu in the consensus catalytic sequence in SPC-40 caused a loss of chitinase activity. Furthermore, the chitin-binding groove in SPC-40 is considerably distorted owing to unfavourable conformations of several residues, including Trp78, Tyr120, Asp186 and Arg242. Three surface loops, His188,His197, Phe202,Arg212 and Tyr244,Pro260, have exceptionally high B factors, suggesting large-scale flexibility. Fluorescence studies indicate that various sugars bind to SPC-40 with low affinities. [source] | ||||||||||