# Characterizing the structure and function of a bacterial multi-kinase sensory complex

> **NIH NIH F32** · MICHIGAN STATE UNIVERSITY · 2021 · $65,994

## Abstract

Abstract
 Bacteria have an incredible capacity to sense and respond to intra- and extracellular fluctuations in the
environment in order to maintain cellular homeostasis. In bacteria, environmental adaptation is commonly
mediated by two-component systems (TCS) that consist of a sensor histidine kinase (HK) that phosphorylates a
cognate response regulator (RR) in response to signal detection. Upon phosphorylation, the RR can bind to DNA
and alter gene expression to facilitate environmental adaptation. Classical TCS have historically been thought
to signal in a highly linear manner with minimal interaction or cross-regulation with other signaling pathways. A
growing body of data from our group and others provide evidence that an unusual class of histidine kinases,
known as HWE kinases, can form multi-protein signaling complexes, creating a new paradigm in bacterial signal
transduction. These signaling systems can integrate information from numerous environmental inputs to
coordinate an array of physiological responses. In Caulobacter crescentus, one such signaling complex, hereby
referred to as the Alphaproteobacterial signalosome, has been identified to coordinately regulate cellular surface
attachment, a critical initial step in biofilm formation. We have shown that the Alphaproteobacterial signalosome
consists of a) the HWE kinase SkaH that functions as a molecular hub protein, b) the HWE kinase LovK, and c)
the classical HK, SpdS. Individually, LovK and SpdS play critical roles in modulating the general stress response
and stationary phase adaptation. Interestingly, sensory information from LovK and SpdS can be integrated
through the signalosome to modulate cellular adhesion through the downstream transcription factors, RtrA and
RtrB, and the hypothetical protein, RtrC. Preliminary data provides evidence that the signalosome is comprised
of additional HWE and classical HK kinases, suggesting that the sensory complex can integrate a broader range
of signals than previously suspected. The research proposed here takes a multidisciplinary approach to
characterize the structure and function of the HWE signalosome. The first aim will use biochemical approaches
and mass spectrometry to identify molecular partners of SkaH and dissect direct interactions within the
signalosome. The second aim will complement the structural analysis of the signalosome by using biochemical
approaches to analyze the signal flow through the signalosome components. Preliminary evidence suggests that
the hypothetical protein, RtrC, is a cryptic transcription factor that functions as a critical output for the HWE
signalosome. In the third aim, I will characterize the structure and function of RtrC with X-ray crystallography and
fluorescent reporters. Additionally, I will use FRET-based biosensors and motility assays to examine the
regulatory link between RtrC and c-di-GMP signaling. The HWE signalosome serves as a prime model system
for examining how multi-kinase sensory syste...

## Key facts

- **NIH application ID:** 10314187
- **Project number:** 1F32GM141017-01A1
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Maeve McLaughlin
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,994
- **Award type:** 1
- **Project period:** 2021-09-13 → 2023-09-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314187

## Citation

> US National Institutes of Health, RePORTER application 10314187, Characterizing the structure and function of a bacterial multi-kinase sensory complex (1F32GM141017-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10314187. Licensed CC0.

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