Computational design of symmetrical eight-bladed β-propeller proteins

Noguchi, Hiroki, Addy, Christine, Simoncini, David, Wouters, Staf, Mylemans, Bram, Van Meervelt, Luc ORCID: 0000-0003-2186-5209, Schiex, Thomas, Zhang, Kam YJ, Tame, Jeremy RH and Voet, Arnout RD
(2019) Computational design of symmetrical eight-bladed β-propeller proteins. IUCRJ, 6 (Pt 1). pp. 46-55.

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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.

Item Type: Article
Uncontrolled Keywords: bioinformatics, protein structure, computational modelling, molecular simulation, structural biology, WD40 proteins, beta-propeller proteins
Depositing User: Symplectic Admin
Date Deposited: 29 May 2019 15:35
Last Modified: 08 Oct 2023 15:59
DOI: 10.1107/S205225251801480X
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