Structure and signaling mechanism of Helicobacter pylori transducer-like protein D

Abstract

Here, we present the first high-resolution structures of an intact extended coiled-coil signaling system, the chemoreceptor transducer-like protein D (TlpD) from Helicobacter pylori , determined by X-ray crystallography in two crystal forms at 2.4-3.3 [A] resolution and cryo-EM at 4.2 [A] resolution. The structures capture multiple signaling conformations and reveal how small perturbations within the ligand-binding domain are propagated through the extended coiled-coil to regulate the kinase interface more than 140 [A] away. Signal transmission is mediated by a cascade of side-chain rearrangements that coordinate gear-like axial rotation of the interlocked -helices and remodel conformation and order of the distal hairpin tips. These near-atomic resolution structures provide a framework for understanding the mechanisms of long-range allostery and cooperativity in chemoreceptors and, more broadly, information transfer in coiled-coil sensory systems.