The Structure of a Soluble Chemoreceptor Suggests a Mechanism for Propagating Conformational Signals

摘要

Transmembrane chemoreceptors, also known as methyl-accepting chemotaxis proteins (MCPs),ntranslate extracellular signals into intracellular responses in the bacterial chemotaxis system. MCP ligandnbinding domains control the activity of the CheA kinase, situated ∼200 Å away, across the cytoplasmicnmembrane. The 2.17 Å resolution crystal structure of a Thermotoga maritima soluble receptor (Tm14)nreveals distortions in its dimeric four-helix bundle that provide insight into the conformational statesnavailable to MCPs for propagating signals. A bulge in one helix generates asymmetry between subunitsnthat displaces the kinase-interacting tip, which resides more than 100 Å away. The maximum bundlendistortion maps to the adaptation region of transmembrane MCPs where reversible methylation of acidicnresidues tunes receptor activity. Minor alterations in coiled-coil packing geometry translate the bulgendistortion to a >25 Å movement of the tip relative to the bundle stalks. The Tm14 structure disclosesnhow alterations in local helical structure, which could be induced by changes in methylation state and/ornby conformational signals from membrane proximal regions, can reposition a remote domain that interactsnwith the CheA kinase.