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

ABSTRACT: 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 apply it to NCBD, a helical, molten globule–like IDP, as proof of concept. The approach entails the experimental and computational characterization of the protein, its separate secondary structure elements (LEGO building blocks), and their supersecondary combinations. Comparative analysis uncovers sp

SUBMITTER: Luong TDN 

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

REPOSITORIES: biostudies-literature