Computational design of symmetrical eight-bladed β-propeller proteins

IUCrJ

Addy, C.¹  Mylemans, B.²  Wouters, S.³  Noguchi, H.⁴  Simoncini, D.⁵ 

[1]Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro, Yokohama, Kanagawa 230-0045, Japan

[2]Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, 1-7-22 Suehiro, Yokohama, Kanagawa 230-0045, Japan

[3]Laboratory of Biomolecular Architecture, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium

[4]Laboratory of Biomolecular Modelling and Design, Department of Chemistry, KU Leuven, Celestijnenlaan 200G, 3001 Leuven, Belgium

[5]MIAT, Universit de Toulouse, INRA, Castanet-Tolosan, France

关键词: BIOINFORMATICS;    PROTEIN STRUCTURE;    COMPUTATIONAL MODELLING;    MOLECULAR SIMULATION;    STRUCTURAL BIOLOGY;    WD40 PROTEINS;    [BETA]-PROPELLER PROTEINS;   

DOI  :  10.1107/S205225251801480X

学科分类：数学（综合）

来源: International Union of Crystallography

【 摘 要 】

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.

【 授权许可】

CC BY