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.
Original language | English |
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Pages (from-to) | 167-174 |
Number of pages | 8 |
Journal | Nature Structural and Molecular Biology |
Volume | 22 |
Issue number | 2 |
Early online date | 12 Jan 2015 |
DOIs | |
Publication status | Published - Feb 2015 |
Keywords
- Crystallography, X-Ray
- Protein Conformation
- Protein Engineering
- Proteins