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Computational design of symmetrical eight-bladed β-propeller proteins

DOI: 10.1107/S205225251801480X DOI Help

Authors: Hiroki Noguchi (KU Leuven) , Christine Addy (Yokohama City University) , David Simoncini (MIAT, Université de Toulouse) , Staf Wouters (KU Leuven) , Bram Mylemans (KU Leuven) , Luc Van Meervelt (KU Leuven) , Thomas Schiex (MIAT, Université de Toulouse) , Kam Y. J. Zhang (RIKEN) , Jeremy R. H. Tame (Yokohama City University) , Arnout R. D. Voet (KU Leuven)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Iucrj , VOL 6

State: Published (Approved)
Published: November 2018

Open Access Open Access

Abstract: β-Propeller proteins form one of the largest families of protein structures, with a pseudo-symmetrical fold made up of subdomains called blades. They are not only abundant but are also involved in a wide variety of cellular processes, often by acting as a platform for the assembly of protein complexes. WD40 proteins are a subfamily of propeller proteins with no intrinsic enzymatic activity, but their stable, modular architecture and versatile surface have allowed evolution to adapt them to many vital roles. By computationally reverse-engineering the duplication, fusion and diversification events in the evolutionary history of a WD40 protein, a perfectly symmetrical homologue called Tako8 was made. If two or four blades of Tako8 are expressed as single polypeptides, they do not self-assemble to complete the eight-bladed architecture, which may be owing to the closely spaced negative charges inside the ring. A different computational approach was employed to redesign Tako8 to create Ika8, a fourfold-symmetrical protein in which neighbouring blades carry compensating charges. Ika2 and Ika4, carrying two or four blades per subunit, respectively, were found to assemble spontaneously into a complete eight-bladed ring in solution. These artificial eight-bladed rings may find applications in bionanotechnology and as models to study the folding and evolution of WD40 proteins.

Journal Keywords: bioinformatics; protein structure; computational modelling; molecular simulation; structural biology; WD40 proteins; β-propeller proteins

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography

Other Facilities: Photon Factory

Added On: 26/11/2018 14:00


Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)