LA JOLLA, CA April 3, 2011 In the constantly morphing field of protein structure, scientists at The Scripps Research Institute offer yet another surprise: a common "chaperone" protein in cells thought to help other proteins fold has been shown instead to loosen them.
The study was published in the April 3 issue of Nature Structural & Molecular Biology.
The research offers the first structural insights into the shape of a "client" protein in the presence of a helper or "chaperone" protein. Specifically, the study examined the client protein p53 tumor suppressor and its interactions with chaperone heat shock protein 90 (Hsp90).
"It was a real surprise to find that, when bound to Hsp90, p53 is loosened and becomes less ordered, forming a molten globule-like state," said the study's lead investigator, molecular biologist Professor H. Jane Dyson. "This contradicts what everyone thought of as the function of chaperone proteinsto help other proteins fold into a well-defined three-dimensional structure."
The findings add to scientists' new understanding of proteins, now thought not only to constantly change shape to perform different functions, but also to be active when unfolded.
It was once thought that proteins could be active only if they were neatly folded into a compact shape and that this structure defined its function. Then Scripps Research investigators Dyson and Professor Peter Wright, as well as others, discovered that unfolded "disordered" proteins (also known as "intrinsically unstructured proteins") could also be active.
One way these intrinsically disordered proteins act is by folding when they bind to other molecules and performing a function such as potentiating cellular signaling or turning on the transcription of a gene.
The disordered protein might then dissociate from this partner, unfold, and perhaps bind to a different molecule in a new shape. Thus, these protei
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Scripps Research Institute