# EPR Spectroscopic Studies of Membrane Proteins

> **NIH NIH R35** · MIAMI UNIVERSITY OXFORD · 2024 · $388,400

## Abstract

Project Summary/Abstract
Overview of Research in the Lorigan Lab and 5 Year Goals
(Overview): Currently, we have limited structural information on membrane proteins. The Lorigan lab is
interested in developing new biophysical methods to probe the structural and dynamic properties of
integral membrane proteins using state-of-the-art pulsed EPR spectroscopic techniques and membrane
solubilizing polymers. The overall objective is to study membrane proteins with EPR in a lipid bilayer as
opposed to a detergent because it more closely mimics a cell membrane. Several proteins have been
shown to not function or fold up correctly in a micelle when compared to a lipid bilayer. This is
challenging because it is more difficult to express, purify, and conduct biophysical spectroscopic
experiments on membrane proteins in lipid bilayers when compared to micelle or globular systems. My
expertise in membrane protein EPR and sample preparation coupled with the powerful pulsed EPR
instrumentation (DEER and ESEEM) that can measure long range distances has attracted several
significant collaborators with important biological problems. My research lab works directly with several
researchers to dramatically improve the quality of membrane protein sample preparation to yield high
quality DEER data that leads to more accurate structural information. Please see the letters of support.
 The major biological focus of the lab is on investigating the structural and dynamic properties of
integral membrane proteins in the KCNE family which is responsible for the modulation of voltage gated
potassium (Kv) channels including KCNQ1 (Q1). This channel is expressed throughout the body to
regulate physiological functions and mutations in this channel are linked to several diseases such as
Long QT syndrome and other heart diseases. Increased understanding of the molecular underpinnings
of KCNE modulation of potassium channels, specifically Q1, would help expand our understanding of
the etiology of these diseases. We will study three members of the KCNE family: KCNE1(E1),
KCNE3(E3), and KCNE4(E4). We are currently applying state-of-the-art EPR techniques to directly
probe the structural and dynamic properties of Q1, E1, E3, and E4. This information will help us better
understand Q1 regulation.
 The following pertinent biological questions will be answered: Which segments of E3 and E4 are
helical in a lipid bilayer? What is the structure and topology of the KCNE3 and KCNE4 with respect to
the membrane? How does E1 bind and interact with Q1 that is required for function?
(5 Year Goals of the Lab): (1) Develop new biophysical techniques to dramatically improve
structural studies of membrane proteins, (2) Probe the structural and dynamic properties of E3, and E4,
(3) Elucidate the binding mechanism of E1 and Q1 to help us better understand the mechanism of Q1
regulation, and (4) Apply the membrane protein techniques that we develop to investigate the structure
of several biologically impo...

## Key facts

- **NIH application ID:** 10764592
- **Project number:** 2R35GM126935-06
- **Recipient organization:** MIAMI UNIVERSITY OXFORD
- **Principal Investigator:** GARY A LORIGAN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $388,400
- **Award type:** 2
- **Project period:** 2018-05-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764592

## Citation

> US National Institutes of Health, RePORTER application 10764592, EPR Spectroscopic Studies of Membrane Proteins (2R35GM126935-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10764592. Licensed CC0.

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