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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.

SUBMITTER: Park K

PROVIDER: S-EPMC4318719 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Control of repeat-protein curvature by computational protein design.

Park Keunwan K Shen Betty W BW Parmeggiani Fabio F Huang Po-Ssu PS Stoddard Barry L BL Baker David D

Nature structural & molecular biology 20150112 2

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, g ...[more]

PMID: 25580576

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