# AAA+ proteolytic machines

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $491,731

## Abstract

Project Summary/Abstract
Intracellular AAA+ proteases remove toxic, damaged, and unnecessary proteins and participate in
cellular processes that promote health and prevent disease. Because protein synthesis is energetically
expensive and proteolysis is irreversible, protein degradation must be carefully regulated to conserve
cellular resources. Building on our extensive experience in structure-function studies of AAA+
proteases, we will use a combination of structural biology, biochemistry/biophysics, protein engineering,
and molecular genetics to determine how the proteolytic activity of three different AAA+ proteases is
mediated and regulated. For example, for the AAA+ HslUV protease, we will determine how
temperature and substrate binding control autoinhibition by a novel I-domain structure that blocks the
axial pore. For the double-ring ClpAP protease, we will probe the roles of the AAA+ D1 and D2 rings in
protein substrate unfolding and translocation in single-molecule optical trapping experiments. For FtsH,
an essential membrane-bound bacterial AAA+ protease, we will determine the mechanisms that limit
degradation of cytosolic proteins, mediate turnover of an important biosynthetic enzyme, and allow the
HflK/HflC membrane partners to control FtsH activity. The unifying theme of this proposal is
understanding how the common and unique structural features of different AAA+ proteases contribute
to their specialized biological roles.
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## Key facts

- **NIH application ID:** 9896752
- **Project number:** 5R01AI016892-41
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** TANIA A BAKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $491,731
- **Award type:** 5
- **Project period:** 1980-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896752

## Citation

> US National Institutes of Health, RePORTER application 9896752, AAA+ proteolytic machines (5R01AI016892-41). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9896752. Licensed CC0.

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