The Stability Landscape of de novo TIM Barrels Explored by a Modular Design Approach

Sergio Romero-Romero,Miguel Costas,Daniel-Adriano Silva Manzano,Sina Kordes,Erendira Rojas-Ortega,Cinthya Tapia,Yasel Guerra,Sooruban Shanmugaratnam,Adela Rodríguez-Romero,David Baker,Birte Höcker,D Alejandro Fernández-Velasco

Journal of Molecular Biology（2021）

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摘要

•The TIM barrel is a versatile fold to understand structure-stability relationships.•A collection of de novo TIM barrels with improved hydrophobic cores was designed.•DeNovoTIMs are reversible in chemical and thermal unfolding, which is uncommon in TIM barrels.•Epistatic effects play a central role in DeNovoTIMs stabilization.•DeNovoTIMs navigate a previously uncharted region of the stability landscape.

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关键词

de novo protein design,protein folding and stability,stability landscape,non-additive effects,(β/α)8-barrel

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