# Functional diversity of Hsp70 and J-protein chaperone systems

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $382,500

## Abstract

PROJECT SUMMARY/ABSTRACT
 Maintenance of cellular homeostasis requires a fine-tuned balance of many biological processes. Protein
homeostasis is particularly intricate, because it requires maintaining balance amongst biogenesis, folding,
trafficking and degradation of all cellular proteins. A group of ubiquitous proteins, referred to collectively as
molecular chaperones, play active roles in maintaining protein homeostasis by transiently binding to many
different polypeptides. Of these, the Hsp70 chaperone/J-protein co-chaperone systems, which are present in all
major cellular compartments, are the most versatile. They play key roles not only in general homeostasis
networks of protein folding and degradation, but also in core biological processes, often by driving assembly and
disassembly of multimeric complexes.
 The overarching goal of this proposal is to understand the attributes of Hsp70, and its J-protein co-
chaperones, that drive their ability to carry out diverse biological roles. To do so we will use well-developed
Hsp70/J-protein systems that are exceptionally amenable to both genetic and biochemical analysis. Knowledge
generated using these systems will be portable to other organisms, as the Hsp70 and J-proteins being studied
are highly conserved. It will also inform other Hsp70/J-protein systems that are less amenable to experimental
analysis than those we employ as models.
 We are focusing on two major knowledge gaps. First, how Hsp70s interact with biologically relevant
substrates. In the cell, polypeptides with substantial secondary and tertiary structure are Hsp70s' natural
substrates. However, most work dissecting Hsp70's cycle of interaction with substrates has been done using
peptide, because of the difficulty in working with partially folded proteins. Thus, understanding of how Hsp70s
interact with these natural substrates is limited. Second, tethering to sites of action is a major means by which
J-proteins drive Hsp70 function. But, that such tethering has evolved into complex and nuanced modes of
functionality has only recently become evident. We will continue analysis of the eukaryotic ribosome
associated J-protein/Hsp70 system. This system is fundamentally important. It not only plays a first-line role in
de novo protein folding, it has been implicated in monitoring and modulating the translation process itself.

## Key facts

- **NIH application ID:** 9994948
- **Project number:** 5R35GM127009-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** ELIZABETH A CRAIG
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994948

## Citation

> US National Institutes of Health, RePORTER application 9994948, Functional diversity of Hsp70 and J-protein chaperone systems (5R35GM127009-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9994948. Licensed CC0.

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