For the first time, St. Jude scientists have mapped the structure of chaperones. These molecules are found in all cells. Chaperones bind to proteins to prevent them from malfunctioning.
This work reveals how a chaperone attaches to a protein to protect it from going bad and causing disease. A report on this study appeared in Science.
The findings help us understand how the cell defends against mistakes in which proteins can unfold, misfold or form toxic clumps. Before this work, scientists did not know the structural details of how chaperones and their proteins link.
“Proteins are first formed as string-like molecules, but with the help of chaperones fold into the globular shapes that give them specific functions,” said Charalampos Kalodimos, PhD, chair of the St. Jude Department of Structural Biology. “The basic structural knowledge gained by studying a range of chaperones will increase our understanding and may lead to clinical applications.”
Scientists used nuclear magnetic resonance (NMR) spectroscopy to study the protein structure. This tool uses powerful magnetic fields to activate molecules. The molecules then emit signals. By studying those signals, scientists can see the protein’s structure.
Chaperones are over-produced or mutated in cancers and neurodegenerative diseases, altering their structure. For this work, the team looked at a three-part chaperone machine found in every cell, Hsp40-Hsp70-NEF, and its attached client protein.
Besides Kalodimos, other co-authors of the Science paper were Yajun Jiang and Paolo Rossi.
The research was sponsored by the National Institutes of Health (R35 GM122462) and ALSAC, the fundraising and awareness arm of St. Jude.
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