# Allostery in an intrinsically disordered transcription factor

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $336,247

## Abstract

The objective of this project is to understand how transcription factors and other signaling proteins utilize
intrinsic disorder (ID) to facilitate their function. Over the past 3 decades it has become increasingly
clear that rather than existing as static structures, proteins are actually ensembles of sometimes very
different conformational states, and that fluctuations and disorder are critical to function. It is of great
import to know how this is done. Are there unifying principles that connect proteins with different
functions? Here we take advantage of two discoveries by our group, which demonstrates that the
transcription factor glucocorticoid receptor (GR) uses disorder-to-order transitions to facilitate function –
in effect, the energy landscape has ID within its functionally important repertoire. We find that ID regions
communicate both with other ID regions, as well as structured domains. Furthermore, we show that GR
employs thermodynamic frustration, wherein the molecule simultaneously codes for activation and
repression, and that GR controls the degree of the repression by producing different isoforms from
alternative translation start sites. How does GR do this? What are the structural and dynamic
determinants of communication between domains? We will perform binding, stability and in vivo activity
measurements and we will use high-resolution NMR structural and dynamic techniques to characterize
the molecular basis of the observed behavior.

## Key facts

- **NIH application ID:** 9836857
- **Project number:** 5R01GM126130-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** VINCENT J. HILSER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $336,247
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836857

## Citation

> US National Institutes of Health, RePORTER application 9836857, Allostery in an intrinsically disordered transcription factor (5R01GM126130-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9836857. Licensed CC0.

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