# Structural Biology Studies of Ribosome Biogenesis Network

> **NIH NIH R01** · FLORIDA STATE UNIVERSITY · 2020 · $409,113

## Abstract

Description: Ribosome is the evolutionarily conserved molecular machine responsible
for synthesis of proteins. In eukaryotic cells, ribosome is produced in a biophysically
distinct subnuclear compartment, the nucleolus, through a cascade of energy-driven
events. This process underlies a number of genetic diseases and is a major target for
anticancer therapeutics. However, the physical interactions of the network required for
this process remain largely uncharacterized. This application will characterize a key
molecular complex called R2TP that acts early in ribosome production by facilitating
assembly of several ribosome production enzymes. R2TP has a wide client base,
collaborates with a general protein folding chaperone, heat shock protein 90 (Hsp90),
and delivers clients to the nucleolus. The Li laboratory has identified effective methods to
purify, reconstitute, and structurally characterize R2TP and its interaction with a client
protein by use of a powerful set of structural biology and biochemical methods. The long-
term goal is to understand the molecular basis for R2TP/Hsp90-mediated assembly
process and uncover the molecular basis for its function in ribosome production. Two
specific aims are designed to 1) dissect the client binding and release cycle of R2TP and
its regulation by nucleotides and the liquid immiscibility of the nucleolus; 2) characterize
at a molecular level how R2TP impacts pre-ribosome structure purified from yeast cells.
Results of this study promise to reveal new interfacial surfaces for anticancer drugs and
to explain the action of those currently in use. The Li laboratory has assembled a team
of scientists with complementary expertise in x-ray crystallography, high-throughput
electron cryomicroscopy, mass spectrometry, biophysics, and protein biochemistry in
order to maximize the chance of successes while mitigating risks.
Relevance: Ribosome production is accelerated in multiple cancer cells.
Correspondingly, R2TP/Hsp90 and their clients are overexpressed in these cells. More
than fifteen types of anticancer drugs have been investigated or in clinical trials that
target molecules involved in this pathway. Though effective in cell-death assays, the
pharmacological basis of many compounds remains to be explained and some develop
resistance in cells. The proposed research provides a platform to test the actions of
these drugs outside the cell and to target previously unknown sites or processes.

## Key facts

- **NIH application ID:** 9997953
- **Project number:** 5R01GM124622-03
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Hong Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,113
- **Award type:** 5
- **Project period:** 2018-09-10 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997953

## Citation

> US National Institutes of Health, RePORTER application 9997953, Structural Biology Studies of Ribosome Biogenesis Network (5R01GM124622-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9997953. Licensed CC0.

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