# Regulated Proteolysis in Bacteria Development and Stress Response

> **NIH NIH R35** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2024 · $415,988

## Abstract

Project Summary
Regulated proteolysis controls the quality and quantity of proteins. In bacteria, energy dependent proteases
eliminate aberrant proteins by recognizing distinctive marks arising from failed quality control, such as
incorrectly exposed hydrophobic regions of proteins or specific tags attached upon prolonged translational
arrest. These same machines control levels and dynamics of native folded proteins often through recruiting
auxiliary factors to increase selectivity. In this proposed work, we focus on two major energy dependent
proteases systems that are conserved in bacteria where understanding of their mechanistic regulation and
scope is incomplete. The ClpXP protease selectively degrades major regulators during the Caulobacter cell
cycle driven by a dedicated hierarchy adaptors and processes replication factors. Illuminating the molecular
details of how adaptors deliver these substrates will reveal rules of specificity crucial for understanding
programmed degradation. Similarly, the allosteric regulation of the Lon quality control protease by ligands or
substrates is important for its function as a quality control protease, with emerging models suggesting that
dynamic conformational changes can modulate specificity. In addition, findings that Lon can selectively remove
DNA bound proteins support new regulatory roles for this highly conserved protease. By using proteomics,
transposon-sequencing, biochemistry, and genetics to understand how bacteria govern the specificity and
activity of these proteases at a mechanistic and cellular level, we will gain critical insight into pathways that
control normal growth and stress responses in all bacteria.

## Key facts

- **NIH application ID:** 10764562
- **Project number:** 2R35GM130320-06
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Peter Chien
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $415,988
- **Award type:** 2
- **Project period:** 2019-01-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764562

## Citation

> US National Institutes of Health, RePORTER application 10764562, Regulated Proteolysis in Bacteria Development and Stress Response (2R35GM130320-06). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10764562. Licensed CC0.

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