Porous assembly of an antifungal protein mediated by zinc and sulfonato-calix[8]arene

J Struct Biol. 2021 Jun;213(2):107711. doi: 10.1016/j.jsb.2021.107711. Epub 2021 Feb 23.

Abstract

Controlled protein assembly holds great potential in the fabrication of biohybrid materials. However, the structural diversity and complexity of proteins present an obstacle to controlled assembly. Supramolecular chemistry is a possible solution as it offers tools to mediate self-assembly with molecular precision. This paper deals with the calixarene- and zinc-mediated assembly and crystallization of the histidine-rich Penicillium chrysogenum antifungal protein B (PAFB). We report crystal structures of pure PAFB, PAFB in complex with Zn2+, and the ternary complex of PAFB, Zn2+ and sulfonato-calix[8]arene (sclx8). A comparison of the three crystal structures revealed the structural plasticity of PAFB. While the flexible and highly anionic sclx8 resulted in large molecular weight aggregates of PAFB in solution, diffraction-quality crystals of PAFB-sclx8 were not obtained. We report crystals of PAFB-Zn2+-sclx8 in which a trinuclear zinc cluster occurred adjacent to a calixarene binding site. Interestingly, the combination of sclx8 complexation and zinc coordination resulted in a porous framework with channels of circa 2 nm diameter. Detailed analysis of the crystal structure highlighted novel molecular recognition features. This research enriches the set of supramolecular interactions available to promote protein assembly.

Keywords: Assembly; Biohybrid; Framework; Macrocycle; Porosity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemistry*
  • Bacterial Proteins / chemistry*
  • Calixarenes / chemistry*
  • Crystallization
  • Crystallography, X-Ray
  • Models, Molecular
  • Penicillium chrysogenum / chemistry
  • Porosity
  • Protein Conformation
  • Solutions
  • Zinc / chemistry*

Substances

  • Antifungal Agents
  • Bacterial Proteins
  • Solutions
  • calix(8)arenesulfonate
  • Calixarenes
  • Zinc