MicroReview: Functional similarities among two‐component sensors and methyl‐accepting chemotaxis proteins suggest a role for linker region amphipathic helices in transmembrane signal transduction

Abstract

SummarySignal-responsive components of transmembrane signal-transducing regulatory systems include methyl-accepting chemotaxis proteins and membrane-bound, two-component histidine kinases. Prokaryotes use these regulatory networks to channel environmental cues into adaptive responses. A typical network is highly discriminating, using a speci®c phosphoryl relay that connects particular signals to appropriate responses. Current understanding of transmembrane signal transduction includes periplasmic signal binding with the subsequent conformational changes being transduced, via transmembrane helix movements, into the sensory protein's cytoplasmic domain. These induced conformational changes bias the protein's regulatory function. Although the mutational analyses reviewed here identify a role for the linker region in transmembrane signal transduction, no speci®c mechanism of linker function has yet been described. We propose a speculative, mechanistic model for linker function based on interactions between two putative amphipathic helices. The model attempts to explain both mutant phenotypes and hybrid sensor data, while accounting for recognized features of amphipathic helices.

Campylobacter jejuni proteins Cj0952c and Cj0951c affect chemotactic behaviour towards formic acid and are important for invasion of host cells

“…In this way, the HAMP domain serves as a linker region that is suggested to be conserved in histidine kinases, adenylyl cyclases, methylaccepting chemotaxis proteins and phosphatases, and converts ligand-induced conformational changes into kinase-controlling signals (Aravind & Ponting, 1999;Butler & Falke, 1998;Le Moual & Koshland, 1996;Williams & Stewart, 1999). Cj0951c shows strong homologies to the cytoplasmic signalling domains of MCPs, being composed of an adaptation region with methylation sites, a flexible region with a conserved glycine hinge, and a protein-interaction region for binding of the chemotaxis protein CheW and the kinase CheA (Hazelbauer et al, 2008).…”

Bacterial chemoreceptors: high-performance signaling in networked arrays

“…Sequence conservation is more subtle among HAMP modules [42,45] but 3D structure is probably shared for the approximately two-thirds of all chemoreceptors that contain the module [43]. There is substantial variation in the sequence and in the deduced 3D organization among transmembrane sensing modules, but the antiparallel four-helix bundle seems to be the most common structure [65] and this structure can be conserved even with minimal sequence identity [66].…”

“…A recent advance comes from nuclear magnetic resonance (NMR) characterization of an isolated HAMP domain from an archaeal, hyperthermophilic, transmembrane protein of unknown function [43] (Box 3). HAMP domains, characterized by two amphiphilic helices joined by a linker [44], occur in many bacterial signaling proteins [42,45]. Typically, HAMP domains are located between transmembrane and cytoplasmic signaling regions of known or putative transmembrane receptors, consistent with a role in converting ligand-induced conformational changes into kinase-controlling signals.…”

Stimulus Perception in Bacterial Signal-Transducing Histidine Kinases

“…This prototypic domain organization can be varied by inclusion of "linker" regions, such as the HAMP or PAS domain (12,276), between TMR2 and the transmitter domain or by additional phosphorylation domains downstream of the transmitter domain (Fig. 2).…”