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• W1526003658 startingPage "147" @default.
• W1526003658 abstract "The pituitary hormones growth hormone (GH), prolactin (PRL) and placental lactogen (PL), are members of an extensive cytokine superfamily of hormones and receptors that share many of the same general structure-function relationships in expressing their biological activities. The biology of the pituitary hormones involves a very sophisticated interplay of cross-reactivity and specificity. Biological activity is triggered via a hormone-induced receptor homodimerization process that is regulated by tertiary features of the hormone. These hormones have an asymmetric four α -helical bundle structure that gives rise to two receptor binding sites that have distinctly different topographies and electrostatic character. This feature plays an important role in the regulation of these systems by producing binding surfaces with dramatically different binding affinities to the receptor extracellular domains (ECD). As a consequence, the signaling complexes for systems that activate through receptor homodimerization are formed in a controlled sequential step-wise manner. Extensive biochemical and biophysical characterization of the two hormone-receptor interfaces indicate that the energetic properties of the two binding sites are fundamentally different and that the receptor shows extraordinary conformational plasticity to mate with the topographically dissimilar sites on the hormone. An unexpected finding has been that the two hormone binding sites are allosterically coupled; a certain set of mutations in the higher affinity site can produce both conformational and energetic effects in the lower affinity site. These effects are so large that at some level they must have played some role in the evolution of the molecule." @default.
• W1526003658 created "2016-06-24" @default.
• W1526003658 creator A5060281780 @default.
• W1526003658 date "2004-01-01" @default.
• W1526003658 modified "2023-10-17" @default.
• W1526003658 title "The Structural Basis for Biological Signaling, Regulation, and Specificity in the Growth Hormone–Prolactin System of Hormones and Receptors" @default.
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• W1526003658 doi "https://doi.org/10.1016/s0065-3233(04)68005-3" @default.
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