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A modular approach to map out the conformational landscapes of unbound intrinsically disordered proteins.

ABSTRACT: SignificanceIntrinsically disordered proteins have the unique ability to morph in response to multiple partners and thereby process sophisticated inputs and outputs. It is, however, a mystery whether their response is passive, that is, entirely determined by the partner, or controlled via an internal, yet unknown, folding mechanism. Here we introduce an approach to examine this key question and demonstrate its potential by dissecting the conformational properties of the partially disordered protein NCBD and obtaining important clues about how it performs its biological function.

SUBMITTER: Luong TDN

PROVIDER: S-EPMC9191344 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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A modular approach to map out the conformational landscapes of unbound intrinsically disordered proteins.

Luong Thinh D N TDN Nagpal Suhani S Sadqi Mourad M Muñoz Victor V

Proceedings of the National Academy of Sciences of the United States of America 20220603 23

Intrinsically disordered proteins (IDPs) fold upon binding to select/recruit multiple partners, morph around the partner's structure, and exhibit allostery. However, we do not know whether these properties emerge passively from disorder, or rather are encoded into the IDP's folding mechanisms. A main reason for this gap is the lack of suitable methods to dissect the energetics of IDP conformational landscapes without partners. Here we introduce such an approach that we term molecular LEGO, and a ...[more]

PMID: 35658083

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