Principles for designing proteins with cavities formed by curved b sheets

Enrique Marcos, Benjamin Basanta, Tamuka M. Chidyausiku, Yuefeng Tang, Gustav Oberdorfer, Gaohua Liu, G. V.T. Swapna, Rongjin Guan, Daniel Adriano Silva, Jiayi Dou, Jose Henrique Pereira, Rong Xiao, Banumathi Sankaran, Peter H. Zwart, Gaetano T. Montelione, David Baker*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Active sites and ligand-binding cavities in native proteins are often formed by curved b sheets, and the ability to control b-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 a 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.

Original languageEnglish
Article number6321
JournalScience
Volume355
Issue number6321
DOIs
Publication statusPublished - 13 Jan 2017

ASJC Scopus subject areas

  • General

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