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

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 ?-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.

SUBMITTER: Moosa MM

PROVIDER: S-EPMC4286261 | biostudies-other | 2015 Jan

REPOSITORIES: biostudies-other

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

Moosa Mahdi Muhammad MM Ferreon Allan Chris M AC Deniz Ashok A AA

Chemphyschem : a European journal of chemical physics and physical chemistry 20141024 1

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 compar ...[more]

PMID: 25345588

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