# Structure/function analysis of understudied pH-sensitive Kir4.2 channels in vitro with conformation specific nanobodies

> **NIH NIH R03** · WASHINGTON UNIVERSITY · 2021 · $157,500

## Abstract

Project Summary
Inward rectifying potassium (Kir) channels regulate excitability in many tissues, and
multiple diseases result from mutations of Kir channel genes. The long-term goal of
this project is to understand the molecular details of understudied pH-sensitive Kir4
sub-family channels. Previously, I defined molecular mechanisms of bulk anionic
lipid regulation of Kir2 channels. These previous studies were made possible by my
establishing a new expression system and purification protocols for eukaryotic Kir2
channels, as well as uniquely combining the multiple methods of (1) computational
docking simulations, (2) functional assays of purified proteins reconstituted in
synthetic liposomes, and (3) high resolution structure determination. These studies
provide a template for gaining new understanding of understudied pH-sensitive Kir4
channels at the molecular level. We will establish an efficient expression system
and a purification protocol for large scale purifications of Kir4.2 homo- and
Kir4.2/Kir5.1 hetero-tetramer proteins that are understudied as well as develop
nanobodies specific to functional states that will not only facilitate structure
determinations in certain functional states but also have therapeutic potentials.
Once established, we will utilize the same `triple combination' of approaches to
determine molecular details of these understudied channel regulation and function.

## Key facts

- **NIH application ID:** 10217510
- **Project number:** 1R03TR003670-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Sun Joo Lee
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $157,500
- **Award type:** 1
- **Project period:** 2021-04-15 → 2022-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217510

## Citation

> US National Institutes of Health, RePORTER application 10217510, Structure/function analysis of understudied pH-sensitive Kir4.2 channels in vitro with conformation specific nanobodies (1R03TR003670-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10217510. Licensed CC0.

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