The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Changes in conformation and stability upon formation of complexes of erythropoietin (EPO) and soluble EPO receptor.

Erythropoietin (EPO) is a glycoprotein hormone which belongs to the four-helical-bundle cytokine family and regulates the level of circulating red blood cells. The EPO receptor (EPOR) belongs to the cytokine-receptor family of proteins. While many of the downstream events following receptor/ligand interaction have been defined, both ligand-induced receptor dimerization and conformational changes induced by binding have been implicated as the initial step in signal transduction. In a recent paper [Philo et al. (1996), Biochemistry 38, 1681-1691] we described the formation of both 1:1 and 2:1 EPOR/EPO complexes. In this paper, we examine changes in protein conformation and stability resulting from the formation of both 1:1 and 2:1 complexes of the soluble extracellular domain of EPOR and the recombinant EPO derived from either Chinese hamster ovary cells or from Escherichia coli cells. Occupation of the first binding site results in a slight conformational change that is apparent in both the far- and near-UV circular dichroism spectra. Formation of the 2:1 complex results in an even greater change in conformation which involves the local environment of one or more aromatic amino acids, accompanied perhaps by a small increase in helical content of the complex. This change in local conformation could occur in the EPO molecule, in the EPOR, in both EPOR molecules due to dimerization, or in all molecules in the trimer. The 1:1 complex exhibits increased stability to thermal-induced denaturation relative to the individual protein component; indeed, the E. coli-derived (nonglycosylated) EPO stays folded in the complex at temperatures where the EPO alone would have unfolded and precipitated. Glycosylation of the receptor increases the reversibility of thermal denaturation, but does not affect the temperature at which this unfolding reaction occurs.[1]

References

 
WikiGenes - Universities