# Dynamics and allostery in protein-RNA regulation

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $427,082

## Abstract

Project Summary/Abstract:
This proposal focuses on two phenomena of widespread importance in biology:
(1) Allostery in regulation of homo-oligomeric proteins. Homo-oligomeric proteins are widespread
and over-represented in regulatory systems. Allosteric communication between ligand binding sites is
critical for effective regulation, and understanding mechanisms of allosteric coupling between the
subunits (protomers) of homo-oligomers is critical for manipulating biological regulation, and as a
means of enabling targeted drug design. However, despite decades of study of allosteric phenomena,
the atomic-level linkages between dynamics, thermodynamics and structure remain enigmatic.
(2) How proteins remodel noncoding RNA to regulate their function. Proteins play critical roles in
proper folding and assembly of structured RNAs, enabling functions that include ribosomal assembly,
RNA catalysis and transcriptional regulation. The RNA folding problem is significant because local
base pairing and stacking interactions in single stranded RNA enable it to fold into many alternative
conformations. Protein-mediated RNA remodeling is particularly important for understanding the
function of regulatory RNAs, yet the mechanisms by which proteins can bias the folding free energy
landscape are largely a mystery.
We propose investigations of the homo-undecameric (11-mer) ring-forming Bacillus trp RNA binding
attenuation protein (TRAP), its interactions with its activator ligand, tryptophan (Trp), its regulatory
target, the trp leader RNA, and inhibitor protein Anti-TRAP. TRAP serves as a sensor of intracellular
tryptophan metabolites (Trp), which can bind its 11 identical sites, activating it for binding to specific
RNA sequences in the 5' untranslated region of the trp operon. RNA binding by Trp-activated TRAP
results in remodeling of RNA secondary structures implicated in regulating transcription via aborted
transcripts (termination). Because of its homo-oligomeric structure and heteromeric interactions, TRAP
is an exceptional model system for studying mechanisms of both homotropic and heterotropic
allosteric regulation.
The aims are to (1) Determine the mechanisms of allosteric communication in the homo-oligomeric
ligand binding protein TRAP, and (2) Elucidate the role of TRAP-dependent RNA folding in regulating
transcription of the trp operon. The aims will be pursued by a combination of structural,
thermodynamic, kinetic and biochemical experiments, including NMR spectroscopy, calorimetry, native
mass spectrometry, co-transcriptional chemical structure probing, and in vivo and in vitro biochemical
assays.

## Key facts

- **NIH application ID:** 9878871
- **Project number:** 5R01GM120923-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** MARK P. FOSTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $427,082
- **Award type:** 5
- **Project period:** 2017-06-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878871

## Citation

> US National Institutes of Health, RePORTER application 9878871, Dynamics and allostery in protein-RNA regulation (5R01GM120923-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9878871. Licensed CC0.

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