Computational design of symmetrical eight-bladed β-propeller proteins

April 9, 2019

Title

Computational design of symmetrical eight-bladed β-propeller proteins

Author

Hiroki Noguchi, Christine Addy, David Simoncini, Staf Wouters, Bram Mylemans, Luc Van Meervelt, Thomas Schiex, Kam Y. J. Zhang, Jeremy R. H. Tame, Arnout R. D. Voet

Year

2018

Journal

IUCrJ

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.

Instrument

J-1500

Keywords

Circular dichroism, Secondary structure, Protein folding, Thermal stability, Thermodynamics, Biochemistry