Principles for designing proteins with cavities formed by curved β sheets

TitlePrinciples for designing proteins with cavities formed by curved β sheets
Publication TypeJournal Article
Year of Publication2017
AuthorsMarcos, Enrique, Basanta Benjamin, Chidyausiku Tamuka M., Tang Yuefeng, Oberdorfer Gustav, Liu Gaohua, Swapna G V. T., Guan Rongjin, Silva Daniel-Adriano, Dou Jiayi, Pereira Jose Henrique, Xiao Rong, Sankaran Banumathi, Zwart Peter H., Montelione Gaetano T., and Baker David
JournalScience (New York, N.Y.)
Pagination201 - 206
Date Published01/2017
ISBN Number1095-92030036-8075
Keywords*Protein Conformation, beta-Strand, Catalytic Domain, Crystallography, X-Ray, Ligands, Nuclear Magnetic Resonance, Biomolecular, Protein Binding, Protein Engineering/*methods, Protein Folding

Active sites and ligand-binding cavities in native proteins are often formed by curved β sheets, and the ability to control β-sheet curvature would allow design of binding proteins with cavities customized to specific ligands. Toward this end, we investigated the mechanisms controlling β-sheet curvature by studying the geometry of β 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 β sheets topped with α helices. Nuclear magnetic resonance and crystal structures of the designs closely match the computational models, showing that β-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.

Short TitleScience