Principles for designing proteins with cavities formed by curved ? sheets.

ABSTRACT: Active sites and ligand-binding cavities in native proteins are often formed by curved ? sheets, and the ability to control ?-sheet curvature would allow design of binding proteins with cavities customized to specific ligands. Toward this end, we investigated the mechanisms controlling ?-sheet curvature by studying the geometry of ? sheets in naturally occurring protein structures and folding simulations. The principles emerging from this analysis were used to design, de novo, a series of proteins with curved ? sheets topped with ? helices. Nuclear magnetic resonance and crystal structures of the designs closely match the computational models, showing that ?-sheet curvature can be controlled with atomic-level accuracy. Our approach enables the design of proteins with cavities and provides a route to custom design ligand-binding and catalytic sites.

SUBMITTER: Marcos E 

PROVIDER: S-EPMC5588894 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature