The symmetric designer protein Pizza as a scaffold for metal coordination. Issue 8 (21st March 2021)

• Record Type: Journal Article
• Authors: Vrancken, Jeroen P. M.; Noguchi, Hiroki; Zhang, Kam Y. J.; Tame, Jeremy R. H.; Voet, Arnout R. D.
• Is Part Of: Proteins. Volume 89:Issue 8(2021)
• Page Start: 945
• Page End: 951
• Publication Date: 2021-03-21
• Subjects: biotechnology -- metalloprotein -- protein design -- structural biology; Proteins -- Periodicals; Proteins -- Periodicals; 572.6
• DOI: 10.1002/prot.26072
• Languages: English
• ISSNs: 0887-3585

Abstract

Abstract: Symmetric proteins are currently of interest as they allow creation of larger assemblies and facilitate the incorporation of metal ions in the larger complexes. Recently this was demonstrated by the biomineralization of the cadmium‐chloride nanocrystal via the Pizza designer protein. However, the mechanism behind this formation remained unclear. Here, we set out to investigate the mechanism driving the formation of this nanocrystal via truncation, mutation, and circular permutations. In addition, the interaction of other biologically relevant metal ions with these symmetric proteins to form larger symmetric complexes was also studied. The formation of the initial nanocrystal is shown to originate from steric strain, where His 58 induces a different rotameric conformation on His 73, thereby distorting an otherwise perfect planar ring of alternating cadmium and chlorine ions, resulting in the smallest nanocrystal. Similar highly symmetric complexes were also observed for the other biological relevant metal ions. However, the flexibility of the coordinating histidine residues allows each metal ion to adopt its preferred geometry leading to either monomeric or dimeric β ‐propeller units, where the metal ions are located at the interface between both propeller units. These results demonstrate that symmetric proteins are not only interesting to generate larger assemblies, but are also the perfect scaffold to create more complex metal based assemblies. Such metal protein assemblies may then find applications in bionanotechnology or biocatalysis.