New Tricks for an Old Dimer

The receptor for human growth hormone is poised like scissors to transmit signals across the cell membrane when activated. [Also see Research Article by Brooks et al.] Much of multicellular biology depends on communication through extracellular signaling molecules that bind to membrane receptors and trigger intracellular signaling events and cell behaviors. One of the first paradigm systems for understanding how polypeptide hormones bind and activate their receptors was human growth hormone (hGH). The molecular details of how hGH binds to its receptor and activates components within the cell started to illuminate over 20 years ago based on biophysical, mutational, and high-resolution structural studies showing that a single hGH molecule binds to two identical molecules of the hGH receptor (1, 2). On page 710 of this issue, Brooks et al. (3) propose a fascinating multistep scissor-like mechanical model in which clamping, rotating, tilting, and the splaying apart of different regions of the transmembrane receptor dimer ultimately lead to receptor activation.