# Assembly and Function of Bacterial Chemotaxis Receptor Signaling Complexes

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2021 · $352,861

## Abstract

Project Summary/Abstract
The overall objective of the project is to determine the mechanism by which bacterial chemotaxis receptors
regulate the activity of the central kinase CheA. Bacterial chemotaxis is a well-studied two-component signaling
system and is also essential for infection by some pathogens. Two-component signaling systems are widespread
in prokaryotes but not found in mammals, making chemotaxis proteins potential targets for novel antibiotics.
The specific objective is to determine the molecular details of the interaction between chemoreceptors and CheA,
and how these change to control kinase activity. Chemoreceptors function within large membrane-bound
hexagonal arrays of receptors, CheA, and CheW. Aims 1-2 will investigate native-like functional arrays of the E.
coli Asp receptor cytoplasmic fragment (CF), CheA, and CheW assembled on vesicles. Solid-state NMR
methods for selective detection of protein interfaces and rigid protein regions will determine structure and
structural changes at the receptor/CheA interface. Complementary hydrogen deuterium exchange mass
spectrometry (HDX-MS) experiments will determine how CheA domain interactions and linker flexibility change
with signaling state. Aim 3 will first optimize preparations of functional arrays of intact receptors with CheA and
CheW, and then apply HDX-MS and selected NMR experiments to this more complex sample to discriminate
which signaling-related changes are caused by ligand binding vs receptor methylation (adaptation). These
experiments will test our hypothesis that the receptor cytoplasmic domain is partially disordered, and that
signaling inputs modulate this disorder to control contacts with CheA and kinase activity.
Understanding the mechanism of this key signaling system will yield insights into the roles and mechanisms of
disordered domains in other protein complexes and how these contribute to long-range allosteric processes. The
project will also demonstrate the promise of combining approaches, such as HDX-MS and solid-state NMR, for
advancing mechanistic understanding of the many protein assemblies that play key roles in biology.

## Key facts

- **NIH application ID:** 10169458
- **Project number:** 5R01GM120195-04
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Lynmarie K. Thompson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $352,861
- **Award type:** 5
- **Project period:** 2017-09-19 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169458

## Citation

> US National Institutes of Health, RePORTER application 10169458, Assembly and Function of Bacterial Chemotaxis Receptor Signaling Complexes (5R01GM120195-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10169458. Licensed CC0.

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