# Protein domains interacting with crowders, RNA and other protein domains

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $291,889

## Abstract

Project Summary/Abstract
Now that protein folding is becoming better understood, we can study it in combination with other interactions
that proteins make with biomolecules. Proteins in cells and organisms continuously interact with other
biomolecules, such as RNA. They are also modified with attachments, such as polyethylene glycol (PEG)
molecules that can enhance stability for drug delivery. Finally, domains of larger proteins can interact with one
another, modifying the folding process or leading to undesirable aggregation, which can lead to protein
diseases.
Our long-term objective is to study interactions of proteins with PEG, RNA, and other protein domains, and to
characterize these interactions quantitatively. Within that long-term objective, our specific aims are threefold:
1) PEG is used extensively in the pharmaceutical industry to improve the delivery of protein drugs. We study
how PEG interacts with protein surfaces, so we can figure out the mechanism by which PEG helps stabilize
protein drugs for delivery. We will study several protein systems, including a therapeutic agent for chronic
kidney disease.
2) The spliceosome assembles in the cell nucleus to splice and re-assemble messenger RNA, which is
necessary to take the information to make new proteins from the nucleus to the ribosomes, where proteins are
synthesized. We will study one of the key protein-RNA interactions by making many mutants and comparing
them with a new model we just developed, that we think can predict how strongly protein and RNA will bind.
This will be important for rational design of drugs to interfere with, or repair, protein-RNA interactions.
3) Large proteins contain many domains, and when they fold things can go wrong. We study these interactions
in an expanded phase diagram of pressure and temperature, to better understand their physical origins. We
discovered that folding intermediates, which are structures that are not quite properly folded, can appear and
disappear in this phase diagram. By learning why this happens we can better suppress such intermediates,
which could form harmful aggregates.
To achieve our goals, we are developing new fluorescence assays to rapidly and sensitively detect
interactions. We are expanding the capabilities of our protein pressurization techniques, so we can study
protein under conditions relevant to pressure sterilization of food. And we are making new PEG-labeled
proteins to study how important PEG length and attachment sites really are.

## Key facts

- **NIH application ID:** 9999606
- **Project number:** 5R01GM093318-11
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** MARTIN GRUEBELE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $291,889
- **Award type:** 5
- **Project period:** 2010-05-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999606

## Citation

> US National Institutes of Health, RePORTER application 9999606, Protein domains interacting with crowders, RNA and other protein domains (5R01GM093318-11). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9999606. Licensed CC0.

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