# Structure and functional mechanisms of molecular chaperones and protein kinases

> **NIH NIH R35** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2021 · $753,785

## Abstract

PROJECT SUMMARY
Our lab works on two main directions: first, the determination of the structural and dynamic basis for
the function and assembly of large protein machineries; and second, the determination of the role of
internal protein dynamics in regulating protein activity and allosteric interactions. We propose to use
NMR spectroscopy, together with other biochemical and biophysical techniques, to determine at the
atomic resolution the mechanisms underpinning the function of two important protein families:
molecular chaperones and protein kinases.
Molecular chaperones are central to maintaining a functional proteome in the cell by rescuing non-
native proteins from aggregation and misfolding and assisting with their folding. Our lab reported the
first ever high resolution structures of molecular chaperones in complex with unfolded proteins. We
will determine the structures of important chaperones such as the Hsp40, Hsp70 and Hsp90 in
complex with client proteins. We wish to address how different chaperones engage non-native
proteins and how distinct chaperone architectures may alter activity.
The Abl kinase holds a prominent place among the over 500 protein kinases encoded by the human
genome. Abl mediates its function by participating in a number of biological processes, including
actin remodeling, cell adhesion and motility, DNA damage response, and bacterial pathogen
response. The Bcr-Abl fusion gene product has constitutive tyrosine kinase activity and causes chronic
myeloid leukemia (CML). We will use NMR to provide fascinating, novel information about the
regulatory and activation mechanisms of this important kinase. We will study how drug-resistance
mutations exert their effect in lowering the drug affinity for Abl.

## Key facts

- **NIH application ID:** 10142492
- **Project number:** 5R35GM122462-06
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** CHARALAMPOS KALODIMOS
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $753,785
- **Award type:** 5
- **Project period:** 2017-05-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142492

## Citation

> US National Institutes of Health, RePORTER application 10142492, Structure and functional mechanisms of molecular chaperones and protein kinases (5R35GM122462-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10142492. Licensed CC0.

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