# Structural dynamics of peptide-translocating ABC transporters

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2020 · $355,274

## Abstract

Protein export across membranes is a critical process for life. In prokaryotes, multiple protein
transport systems were evolved to facilitate the transfer of amphipathic and hydrophilic proteins
of impressive sizes across lipid hydrophobic barriers. The simplest of these systems consist of
an ATP binding Cassette (ABC) transporter which harnesses the energy of ATP hydrolysis to
power the movement of cargo peptides or proteins across the cell membranes. In gram positive
bacteria, ABC transporters export antimicrobial or quorum sensing peptides which serve to
endow the organism with survival advantages under conditions of limited resources. The long
term goal of this application is to illuminate the conformational dynamics of peptidase-containing
ABC transporters (PCATs) which utilizes a built in cysteine protease domain to cleave the signal
sequence of the cargo peptide prior to export. The premise of our strategy is grounded in 1)
recent high resolution structures of PCATs that define their molecular architecture and set the
stage for detailed investigation of the mechanism by which these transporters enable protein
translocation and 2) the track record of the PI in the application of state of the art electron
paramagnetic resonance (EPR) spectroscopy in conjunction with mutagenic analysis to active
transporters. The specific aims are designed to address unanswered questions in the field
including the structural basis of alternating access powered by ATP turnover, the determinants
of cargo protein specificity, and the structure and environment of the cargo protein as it
transitions through the transporter. Over the last decade, our approach integrated with
molecular modeling has been instrumental in revealing the structural dynamics of multidrug
ABC exporters and providing insight into the mechanistic diversity within this family. The
significance of the proposed research stems from a molecular target at the junction of
antibacterial peptide transport, bacterial immunity and represents a fundamental biochemical
process by which proteins are exported across lipid bilayers.

## Key facts

- **NIH application ID:** 10000109
- **Project number:** 5R01GM128087-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Hassane S Mchaourab
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $355,274
- **Award type:** 5
- **Project period:** 2019-08-21 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000109

## Citation

> US National Institutes of Health, RePORTER application 10000109, Structural dynamics of peptide-translocating ABC transporters (5R01GM128087-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000109. Licensed CC0.

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