TY - JOUR
T1 - Principles for designing proteins with cavities formed by curved b sheets
AU - Marcos, Enrique
AU - Basanta, Benjamin
AU - Chidyausiku, Tamuka M.
AU - Tang, Yuefeng
AU - Oberdorfer, Gustav
AU - Liu, Gaohua
AU - Swapna, G. V.T.
AU - Guan, Rongjin
AU - Silva, Daniel Adriano
AU - Dou, Jiayi
AU - Pereira, Jose Henrique
AU - Xiao, Rong
AU - Sankaran, Banumathi
AU - Zwart, Peter H.
AU - Montelione, Gaetano T.
AU - Baker, David
PY - 2017/1/13
Y1 - 2017/1/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85009786943&partnerID=8YFLogxK
U2 - 10.1126/science.aah7389
DO - 10.1126/science.aah7389
M3 - Article
C2 - 28082595
AN - SCOPUS:85009786943
SN - 0036-8075
VL - 355
SP - 201
EP - 206
JO - Science
JF - Science
IS - 6321
ER -