# Intracellular Signaling by Bacterial Chemoreceptors

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $583,877

## Abstract

Project Summary
Chemotactic behaviors, movements toward or away from chemicals in an organism’s environment, play
important roles in the lives of bacteria. Chemotaxis enables microbes to form communities such as
biofilms, to find and colonize host organisms, and to successfully carry out complex, multi-host life
cycles. Better understanding of how bacteria detect and respond to their chemical environment will
play an important role in the development of new therapeutic strategies for preventing and treating
bacterial infections. The long-term goal of this project is to elucidate, in molecular detail, the in vivo
signaling mechanisms of the transmembrane receptors that mediate chemotactic behavior in E. coli, a
model system for chemotaxis studies.
The serine chemoreceptor Tsr forms stable ternary complexes with two cytoplasmic proteins – a
histidine autokinase (CheA) and a scaffolding protein (CheW) that couples CheA activity to
chemoreceptor control. These signaling complexes are organized into highly cooperative arrays,
typically located at the cell poles, that detect chemical stimuli with high sensitivity over a wide range of
concentrations. The overall objectives of the next project period are to elucidate the mechanisms of
signal transmission through chemoreceptor molecules and how those ligand-induced conformational
changes modulate CheA activity in receptor signaling complexes.
Our overall working hypothesis about signal transmission within chemoreceptor molecules proposes
that its structural subelements – external ligand-binding domain, transmembrane helices, HAMP and
methylation helix bundles, and cytoplasmic hairpin tip that interacts directly with CheW and CheA –
transmit and process sensory information through shifts in their dynamic behaviors and stabilities.
Neighboring elements are coupled in opposition, such that destabilizing inputs to one element produce
stabilizing responses in the other. The interplay of these opposing structural forces poises the receptor
molecule to detect and respond to small stimulus inputs.
The project will test these signaling ideas by exploiting in vivo crosslinking assays to detect and to trap
different output-related structures in Tsr and CheA molecules. We will characterize the signaling
properties of mutant or crosslinked proteins with in vivo serine dose-response assays based on Förster
Resonance Energy Transfer (FRET). Collaborations with other groups will provide molecular dynamics
simulations to assess the structural and dynamics changes in mutant signaling proteins and cryo-
electron microscopy to examine structural features of mutant receptor arrays at enhanced resolution.

## Key facts

- **NIH application ID:** 10842396
- **Project number:** 5R01GM019559-51
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** JOHN S PARKINSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $583,877
- **Award type:** 5
- **Project period:** 1991-06-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842396

## Citation

> US National Institutes of Health, RePORTER application 10842396, Intracellular Signaling by Bacterial Chemoreceptors (5R01GM019559-51). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10842396. Licensed CC0.

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