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Chemphyschem. 2015 Jan 12;16(1):90-4. doi: 10.1002/cphc.201402661. Epub 2014 Oct 24.

Forced folding of a disordered protein accesses an alternative folding landscape.

Author information

1
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037 (USA).

Abstract

Intrinsically disordered proteins (IDPs) are involved in diverse cellular functions. Many IDPs can interact with multiple binding partners, resulting in their folding into alternative ligand-specific functional structures. For such multi-structural IDPs, a key question is whether these multiple structures are fully encoded in the protein sequence, as is the case in many globular proteins. To answer this question, here we employed a combination of single-molecule and ensemble techniques to compare ligand-induced and osmolyte-forced folding of α-synuclein. Our results reveal context-dependent modulation of the protein's folding landscape, suggesting that the codes for the protein's native folds are partially encoded in its primary sequence, and are completed only upon interaction with binding partners. Our findings suggest a critical role for cellular interactions in expanding the repertoire of folds and functions available to disordered proteins.

KEYWORDS:

biophysics; intrinsically disordered proteins; protein folding; protein-ligand interactions; single-molecule FRET

PMID:
25345588
PMCID:
PMC4286261
DOI:
10.1002/cphc.201402661
[Indexed for MEDLINE]
Free PMC Article

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