基因,蛋白,免疫 课程之蛋白组学 3.pdf

JOURNAL OF MOLECULAR RECOGNITION J. Mol. Recognit. 1999;12:355–362 Molecular recognition events involved in the activation of the growth hormone receptor by growth hormone Stuart N. Behncken and Michael J. Waters* Department of Physiology and Pharmacology and Centre for Molecular and Cellular Biology, University of Queensland, St Lucia 4072, Australia Binding of growth hormone (GH) to its receptor (GHR) is a well-studied example of molecular recognition between a cytokine and its receptor. Extensive mutagenesis studies and several crystal structures have defined the key interactive amino acid residues that are involved in binding and subsequent receptor dimerization. This review encompasses each of the three molecular recognition events involved in GHR activation, namely binding of GH to its two receptors and the interactions that occur between these receptors. Particular attention is given to species and ligand specificity of hormone binding and to the molecular recognition events involved in receptor activation, including the possibility that a conformational change in the receptor is required. Copyright 1999 John Wiley Sons, Ltd. Keywords: growth hormone; receptor; recognition; dimerization; erythropoietin; signaling Introduction poietin, prolactin and many interleukins (reviewed in Mott and Campbell, 1995). Although these proteins share little The efficacy of the endocrine system relies on the sequence homology, their helices are arranged in a highly exquisitely specific lock and key fit of a hormone for its