# Regulation mechanisms of ABS transporters

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $65,851

## Abstract

PROJECT SUMMARY
This proposal seeks to understand how proteins located in the cell membrane work as gatekeepers to
selectively allow compounds into or out of the cell. Such gatekeepers are known as or ATP-binding
cassette (ABC) transporters, because they use the energy of ATP (adenosine triphosphate) hydrolysis
to transport compounds across the cell membrane. Bacterial ABC importers are essential for organism
survival, controlling the rate of uptake for nutrients scavenged from the bacterium’s environment.
Control of the rate of transport precludes over-accumulation of a nutrient that is beneficial at low
concentrations, but is potentially toxic at high concentrations. While a subset of ABC proteins contain
an additional “accessory” domain that can regulate the uptake of compounds by shutting off the
transporter, it is unclear why certain transporters contain these domains while others do not. However,
we do understand that certain transporters are “turned off” when a specific compound or protein binds
to this accessory domain. Other accessory domains regulate by “sensing” changes in the
microenvironment and reacting accordingly. To decipher this mechanism of regulation, the PI’s
laboratory combines biochemical and biophysical experiments with structural biology to understand how
these accessory domains play a role in transport regulation, which in restricts or allows nutrients to
enter the cell. This research program will define the molecular mechanism that controls nutrient uptake
and allow researchers to understand how multiple transport systems work in concert within an organism
to maintain cell survival. We will test our hypothesis that regulation of transporter activation via a sensing
accessory protein. The proposed research will decipher the complex circuitry of regulation in a model
system in three Aims to: (1) understand how PepT SBPs select for different substrates within the
microenvironment (i.e., nutrients, cofactors and peptides); (2) determine how the assembly of the core
transporter dictates transport selectivity and efficiency (3) reveal how PepT transporters regulate the
import of substrates into the cell through the activation of a novel regulatory domain. This research
program has set out to close critical gaps in the understanding of the fundamentals of the transport
mechanism present in all bacteria. The results will yield insights into how regulatory domains modulate
transport across all organisms, crucial for cell viability.

## Key facts

- **NIH application ID:** 11100897
- **Project number:** 3R01GM140584-05S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Heather Wendy Pinkett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $65,851
- **Award type:** 3
- **Project period:** 2020-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11100897

## Citation

> US National Institutes of Health, RePORTER application 11100897, Regulation mechanisms of ABS transporters (3R01GM140584-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11100897. Licensed CC0.

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