# Molecular Mechanisms of Channels and Transporters

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $466,500

## Abstract

ABSTRACT
Knowledge of protein motion is necessary to bridge the gap between structure and function and gain insight
into the molecular mechanism of protein machines. My lab studies the function of ion channels and ion-coupled
transporters, integral membrane proteins that must undergo structural transitions to regulate the flow of ions
(channels) or actively pump substrates (transporters) across biological membrane barriers. A set of distinct but
interrelated projects examines the mechanism of secondary active transport, promiscuous multidrug
recognition, ion channel selectivity and gating, molecular basis of temperature sensing, allosteric regulation of
transporter and channel activity, and how small localized interactions can regulate broader dynamics in
membrane proteins. These research questions span time- and length- scales, requiring an array of
experimental approaches and a well-developed set of model systems to enable hypothesis driven research.
One of our primary tools is NMR spectroscopy, which can simultaneously provide structural, thermodynamic
(populations), and kinetic (rates of transitions) data with site-specific resolution. NMR chemical shifts are also
highly sensitive to changes in the local environment, providing a direct readout of proton binding, a process
that is otherwise difficult to monitor experimentally but central to dissecting proton-coupled transport. Over the
past 10 years, my lab has done the painstaking work necessary to develop three completely independent
model transporter and channel systems (EmrE, NaK, Shaker-VSD) and establish experimental tools ranging
from NMR and molecular biophysics to in vitro and in vivo functional assays. We are now primed to address
essential research questions that probe the molecular mechanism of these specific systems but also have
broader implications for understanding how protein conformational change is regulated, promiscuity versus
specificity in substrate recognition, the complexity of proton-coupled transport, and molecular basis for
allosteric regulation of protein function.

## Key facts

- **NIH application ID:** 10834148
- **Project number:** 5R35GM141748-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Katherine Anne Henzler-Wildman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $466,500
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834148

## Citation

> US National Institutes of Health, RePORTER application 10834148, Molecular Mechanisms of Channels and Transporters (5R35GM141748-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10834148. Licensed CC0.

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