Computational design of symmetrical eight-bladed β-propeller proteins

Noguchi, H, Addy, C, Simoncini, D, Wouters, S, Mylemans, B, Van Meervelt, L ORCID: 0000-0003-2186-5209, Schiex, T, Zhang, KYJ, Tame, JRH and Voet, ARD (2019) Computational design of symmetrical eight-bladed β-propeller proteins Iucrj, 6 (Pt 1). pp. 46-55. ISSN 2052-2525, 2052-2525

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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.

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:	01 Mar 2026 02:50
DOI:	10.1107/S205225251801480X
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3043312
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