Structure of the growth hormone-receptor complex and mechanism of receptor signaling.

Abstract

The structure of the growth hormone-receptor complex discussed here is the first such system to be studied at the level of atomic detail and provides unique information that elucidates the mechanism of signal transduction of an important receptor family. The growth hormone receptor is a single-pass receptor, with an extracellular protein domain, a transmembrane domain and an intracellular protein domain. Structural data, obtained by crystallography, indicate that there are actually two growth hormone receptors that encapsulate the bound hormone. Although the topology of the hormone is asymmetric, the receptors can use their same sequence of residues to bind to different structural motifs by changing conformation. This mechanism of aggregation controls signal transduction. It may be possible to use this information in the design of radiolabeled ligands for molecular nuclear medicine studies involving the concentration or occupancy of growth receptors.