# Protein Folding in the Eukaryotic Cytosol

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $485,977

## Abstract

The long term goal of this Research Program is to understand how newly translated
proteins fold in eukaryotic cells. The proposed research will focus on folding events as
they occur at the ribosome during synthesis of a polypeptide and will examine the role of
molecular chaperones in their folding process. The conceptual framework for
understanding de novo protein folding originates from our work in the previous funding
cycle, which showed that a network of chaperones named CLIPS (Chaperones Linked to
Protein Synthesis) is physically and functionally linked to the translation machinery. Our
working hypothesis is that the CLIPS chaperones are tasked with guiding newly
synthesized polypeptides to their folded conformation. Chaperone-mediated folding
pathways appear to involve the cooperation of different classes of CLIPS, including
chaperones that act early in the folding process, such as the Nascent Chain Associated
Complex (NAC), the Hsp70 proteins and the GIM/prefoldin complex, and the
mechanistically distinct chaperone TRiC/CCT, which appears to act later in the folding
process. Our general strategy to elucidate how chaperones mediate the folding of newly
synthesized proteins relies on the close integration of in vitro and in vivo approaches with
computational biology analyses. Our proposed experiments are aimed at obtaining
functional, mechanistic and structural insights into the role of chaperones in de novo
folding.

## Key facts

- **NIH application ID:** 10667993
- **Project number:** 2R01GM056433-24
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Judith Frydman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $485,977
- **Award type:** 2
- **Project period:** 1997-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10667993

## Citation

> US National Institutes of Health, RePORTER application 10667993, Protein Folding in the Eukaryotic Cytosol (2R01GM056433-24). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10667993. Licensed CC0.

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