title: Control of repeat-protein curvature by computational protein design.
abstract: Shape complementarity is an important component of molecular recognition, and the ability to precisely adjust the shape of a binding scaffold to match a target of interest would greatly facilitate the creation of high-affinity protein reagents and therapeutics. Here we describe a general approach to control the shape of the binding surface on repeat-protein scaffolds and apply it to leucine-rich-repeat proteins. First, self-compatible building-block modules are designed that, when polymerized, generate surfaces with unique but constant curvatures. Second, a set of junction modules that connect the different building blocks are designed. Finally, new proteins with custom-designed shapes are generated by appropriately combining building-block and junction modules. Crystal structures of the designs illustrate the power of the approach in controlling repeat-protein curvature.
authors.affiliation: 1] Department of Biochemistry, University of Washington, Seattle, Washington, USA. [2] Institute for Protein Design, University of Washington, Seattle, Washington, USA.
authors.forename: Keunwan
authors.initials: K
authors.lastname: Park
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Betty W
authors.initials: BW
authors.lastname: Shen
authors.affiliation: 1] Department of Biochemistry, University of Washington, Seattle, Washington, USA. [2] Institute for Protein Design, University of Washington, Seattle, Washington, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Parmeggiani
authors.affiliation: 1] Department of Biochemistry, University of Washington, Seattle, Washington, USA. [2] Institute for Protein Design, University of Washington, Seattle, Washington, USA.
authors.forename: Po-Ssu
authors.initials: PS
authors.lastname: Huang
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Barry L
authors.initials: BL
authors.lastname: Stoddard
authors.affiliation: 1] Department of Biochemistry, University of Washington, Seattle, Washington, USA. [2] Institute for Protein Design, University of Washington, Seattle, Washington, USA. [3] Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baker
mesh_terms: D018360:Crystallography, X-Ray; D000090263:Leucine-Rich Repeat Proteins; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods; D011506:Proteins / Q000737:chemistry*
chemical_list: D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins