title: Principles for designing proteins with cavities formed by curved β sheets.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.|Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.|Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Marcos
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.|Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.|Graduate Program in Biological Physics, Structure, and Design, University of Washington, Seattle, WA 98195, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Basanta
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.|Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.|Graduate Program in Biological Physics, Structure, and Design, University of Washington, Seattle, WA 98195, USA.
authors.forename: Tamuka M
authors.initials: TM
authors.lastname: Chidyausiku
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.|Northeast Structural Genomics Consortium, Piscataway, NJ 08854, USA.
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.|Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.|Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/3, 8010-Graz, Austria.
authors.forename: Gustav
authors.initials: G
authors.lastname: Oberdorfer
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.|Northeast Structural Genomics Consortium, Piscataway, NJ 08854, USA.
authors.forename: Gaohua
authors.initials: G
authors.lastname: Liu
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.|Northeast Structural Genomics Consortium, Piscataway, NJ 08854, USA.
authors.forename: G V T
authors.initials: GV
authors.lastname: Swapna
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.|Northeast Structural Genomics Consortium, Piscataway, NJ 08854, USA.
authors.forename: Rongjin
authors.initials: R
authors.lastname: Guan
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.|Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
authors.forename: Daniel-Adriano
authors.initials: DA
authors.lastname: Silva
authors.affiliation: Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.|Graduate Program in Biological Physics, Structure, and Design, University of Washington, Seattle, WA 98195, USA.|Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Dou
authors.affiliation: Berkeley Center for Structural Biology, Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley Laboratory, Berkeley, CA 94720, USA.|Joint BioEnergy Institute, Emeryville, CA 94608, USA.
authors.forename: Jose Henrique
authors.initials: JH
authors.lastname: Pereira
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.|Northeast Structural Genomics Consortium, Piscataway, NJ 08854, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Joint BioEnergy Institute, Emeryville, CA 94608, USA.
authors.forename: Banumathi
authors.initials: B
authors.lastname: Sankaran
authors.affiliation: Joint BioEnergy Institute, Emeryville, CA 94608, USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Zwart
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.|Northeast Structural Genomics Consortium, Piscataway, NJ 08854, USA.|Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 USA.
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. dabaker@u.washington.edu.|Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.|Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baker
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D000072757:Protein Conformation, beta-Strand; D015202:Protein Engineering / Q000379:methods*; D017510:Protein Folding
chemical_list: D008024:Ligands