# Administrative Supplement for Flow Quench Instrument

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $42,511

## Abstract

Summary/Abstract
The mechanism by which transcription factors assemble active transcription complexes on specific DNA
sequences does not appear to follow a simple recognition code. Subtle, and not-so-subtle, structural changes
occur when DNA binds to transcription factors. Our overall hypothesis is that transcription factor-DNA binding
would instead be better described by similar principles as have been elucidated for the protein folding problem.
We have discovered that the 230 amino acid intrinsically disordered transcription activation domain (TAD) of
NFκB dramatically alters its DNA binding specificity. Because the domain is disordered, we need to measure its
dynamic changes on the millisecond timescale. The best way we know to do this is by Flow Quench coupled to
HDX-MS. We are therefore requesting an equipment supplement to purchase the Flow Quench instrument. This
instrument is expected to reveal subtle changes in the ensemble population of the TAD upon DNA binding to the
DNA-binding domain that had been thought to be decoupled from the TAD. This will be critical to Aim 1 of the
parent R01. We will also use the instrument to determine subtle changes in the TAD upon ternary complex
formation with DNA and RPS3, the transcription co-activator studied in Aim 3. The HDX-MS results will inform
the computational simulations integrated with experiments in the parent grant.

## Key facts

- **NIH application ID:** 10799448
- **Project number:** 3R01GM141182-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** ELIZABETH A. KOMIVES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $42,511
- **Award type:** 3
- **Project period:** 2022-08-19 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799448

## Citation

> US National Institutes of Health, RePORTER application 10799448, Administrative Supplement for Flow Quench Instrument (3R01GM141182-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10799448. Licensed CC0.

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