# Structural and biophysical studies of proteins, nucleic acids, and their complexes

> **NIH NIH R35** · NORTHWESTERN UNIVERSITY · 2024 · $582,907

## Abstract

Project Summary
 The central theme of this proposal is structural and mechanistic studies of nucleic acids, proteins, and
their interactions. The two broad topics that will serve as foci for our future research are: 1) the structure and
mechanism of topoisomerases, and 2) the structure and mechanism of non-coding RNA molecules, particularly
T-box riboswitches. The aim of our work is to discover and explore paradigms that help to illuminate the
structure and mechanism of biological molecules.
 Topoisomerases are ubiquitous proteins found across all three domains of life. They are involved in
several cellular processes and the importance of their cellular role is underscored by the fact that they are the
target of several cancer chemotherapeutic agents and antibiotics. The study of the structure, mechanism, and
function of topoisomerases not only furthers our understanding at many different levels of proteins that interact
with DNA and alter its topological properties, but also provides important information to aid in the design of
new therapeutic agents. We will continue our comprehensive studies of topoisomerases with an emphasis on
three large and complementary sub-projects: i) Single molecule studies of type IA topoisomerases, ii) Structural
studies of topoisomerases on natural substrates, and iii) Structural studies of gyrase in complex with mini-
circle DNA. These sub-projects will help answer crucial questions that are needed to advance the field to the next
level.
 Riboswitches are ligand-specific cis-regulatory RNA elements found in untranslated regions of mRNAs
that respond to defined external signals to affect transcription or translation of downstream genes. Bacterial T-
box riboswitches represent a unique class of riboswitches that do not bind small molecule ligands, instead they
recognize and bind tRNA molecules and sense directly their aminoacylation state. They represent an excellent
paradigm to understand RNA structure and architecture, recognition of RNA molecules by other RNA molecules,
RNA-based gene regulation, and the evolution of gene regulatory function from the ancient RNA world. We will
continue and expand our studies of T-box riboswitches by concentrating in three subprojects: i) Single molecule
studies of translational T-box riboswitches, ii) Structural and single molecule studies of typical T-box
riboswitches, and iii) Structural studies of tandem T-box riboswitches. These three sub-projects will advance
our understanding of T-box riboswitches and non-coding RNA molecules, molecules that are still not fully
understood at the atomic level.

## Key facts

- **NIH application ID:** 10833068
- **Project number:** 5R35GM118108-07
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Alfonso Mondragon
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $582,907
- **Award type:** 5
- **Project period:** 2017-09-30 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833068

## Citation

> US National Institutes of Health, RePORTER application 10833068, Structural and biophysical studies of proteins, nucleic acids, and their complexes (5R35GM118108-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10833068. Licensed CC0.

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