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Influence of circular permutations on the structure and stability of a six‐fold circular symmetric designer protein

DOI: 10.1002/pro.3961 DOI Help

Authors: Bram Mylemans (KU Leuven) , Hiroki Noguchi (KU Leuven) , Els Deridder (KU Leuven) , Eveline Lescrinier (KU Leuven) , Jeremy R. H. Tame (Yokohama City University) , Arnout R. D. Voet (KU Leuven)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Protein Science

State: Published (Approved)
Published: October 2020
Diamond Proposal Number(s): 17167

Abstract: The β‐propeller fold is adopted by a sequentially diverse family of repeat proteins with apparent rotational symmetry. While the structure is mostly stabilised by hydrophobic interactions, an additional stabilisation is provided by hydrogen bonds between the N‐and C‐termini, which are almost invariably part of the same β‐sheet. This feature is often referred to as the “Velcro” closure. The positioning of the termini within a blade is variable and depends on the protein family. In order to investigate the influence of this location on protein structure, folding and stability, we created different circular permutants, and a circularised version, of the designer propeller protein named Pizza. This protein is perfectly symmetrical, possessing six identical repeats. While all mutants adopt the same structure, the proteins lacking the “Velcro” closure were found to be significantly less resistant to thermal and chemical denaturation. This could explain why such proteins are rarely observed in nature. Interestingly the most common “Velcro” configuration for this protein family was not the most stable among the Pizza variants tested. The circularised version shows dramatically improved stability, which could have implications for future applications.

Journal Keywords: cyclic permutant; protein design; protein stability; β‐propeller

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I03-Macromolecular Crystallography

Other Facilities: X06DA at Swiss Light Source