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Publication - Dr Fabio Parmeggiani

    Control of repeat-protein curvature by computational protein design


    Park, K, Shen, BW, Parmeggiani, F, Huang, P-S, Stoddard, BL & Baker, D, 2015, ‘Control of repeat-protein curvature by computational protein design’. Nature Structural and Molecular Biology, vol 22., pp. 167-74


    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.

    Full details in the University publications repository