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

Research output: Contribution to journalArticleResearchpeer-review

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

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Ligands
Catalytic Domain
Proteins
Protein Folding
Carrier Proteins
Magnetic Resonance Spectroscopy
Binding Sites

ASJC Scopus subject areas

  • General

Cite this

Marcos, E., Basanta, B., Chidyausiku, T. M., Tang, Y., Oberdorfer, G., Liu, G., ... Baker, D. (2017). Principles for designing proteins with cavities formed by curved b sheets. Science, 355(6321), [6321]. https://doi.org/10.1126/science.aah7389

Principles for designing proteins with cavities formed by curved b sheets. / Marcos, 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.; Baker, David.

In: Science, Vol. 355, No. 6321, 6321, 13.01.2017.

Research output: Contribution to journalArticleResearchpeer-review

Marcos, E, Basanta, B, Chidyausiku, TM, Tang, Y, Oberdorfer, G, Liu, G, Swapna, GVT, Guan, R, Silva, DA, Dou, J, Pereira, JH, Xiao, R, Sankaran, B, Zwart, PH, Montelione, GT & Baker, D 2017, 'Principles for designing proteins with cavities formed by curved b sheets' Science, vol. 355, no. 6321, 6321. https://doi.org/10.1126/science.aah7389
Marcos E, Basanta B, Chidyausiku TM, Tang Y, Oberdorfer G, Liu G et al. Principles for designing proteins with cavities formed by curved b sheets. Science. 2017 Jan 13;355(6321). 6321. https://doi.org/10.1126/science.aah7389
Marcos, 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. ; Baker, David. / Principles for designing proteins with cavities formed by curved b sheets. In: Science. 2017 ; Vol. 355, No. 6321.
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