Understanding how external signals are transduced across cellular membranes is a formidable challenge for molecular biologists. Through the structure of an archaeal HAMP domain, which was determined by nuclear magnetic resonance spectroscopy, we gained more insight into this process. The HAMP domain connects extracellular sensory to intracellular effector domains in a large number of transmembrane receptor proteins and hence is thought to play a crucial role in signal transduction. The structure reveals an ability to switch reversibly between two conformations with similar energy levels, whose balance is affected by ligand binding. A cogwheel-like rotation of helices, triggered by ligand binding to the sensory domain, appears to underlie the conformational change that mediates transduction of extracellular information into the cell.