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Cofactor-free oxidase-mimetic nanomaterials from self-assembled histidine-rich peptides

Abstract

Natural oxidases mainly rely on cofactors and well-arranged amino acid residues for catalysing electron-transfer reactions but suffer from non-recovery of their activity upon externally induced protein unfolding. However, it remains unknown whether residues at the active site can catalyse similar reactions in the absence of the cofactor. Here, we describe a series of self-assembling, histidine-rich peptides, as short as a dipeptide, with catalytic function similar to that of haem-dependent peroxidases. The histidine residues of the peptide chains form periodic arrays that are able to catalyse H2O2 reduction reactions efficiently through the formation of reactive ternary complex intermediates. The supramolecular catalyst exhibiting the highest activity could be switched between inactive and active states without loss of activity for ten cycles of heating/cooling or acidification/neutralization treatments, demonstrating the reversible assembly/disassembly of the active residues. These findings may aid the design of advanced biomimetic catalytic materials and provide a model for primitive cofactor-free enzymes.

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Fig. 1: Design of haem-free self-assembling oligohistidine catalysts inspired by natural haem-containing enzymes.
Fig. 2: Structural characterization of the peptide-assembled catalysts.
Fig. 3: Crystal lattice of the peptide nanostructures and peptide chain arrangement patterns.
Fig. 4: Functional characterization of the peptide-assembled catalysts.
Fig. 5: Theoretical model of the catalytic process.
Fig. 6: Externally triggered deactivation and activation of the H15 peptide and HRP.

Data availability

The data that support the findings of this study are available within the paper and its Supplementary Information files. Additional data and files are available from the corresponding authors upon reasonable request.

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Acknowledgements

We are grateful for the financial support from the National Science Foundation of China (21872044, 51761145044, 11422215, 11672079), the Fundamental Research Funds for the Central Universities (XK1806, buctrc201902), the Science Fund for Creative Research Groups of the National Natural Science Foundation of China (21721002), the National Basic Research Programs of China (2016YFA0201601, 2018YFA0208900), the National Science Foundation of Beijing (2184130), the Beijing Municipal Science and Technology Commission (Z191100004819008), the Key Research Program of Frontier Sciences, CAS (QYZDB-SSW-SLH029), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB36000000) and the K. C. Wong Education Foundation (GJTD-2018-03). We also thank L. Jiang from the Institute of Chemistry, CAS, for discussions on crystal models and Y. Liu from the Technical Institute of Physics and Chemistry, CAS, for the EPR analysis.

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Authors

Contributions

Z.G.W. and B.D. conceived and designed the experiments. Q.L., Y.Z., Y.S. and L.D. performed the experiments. Z.G.W., B.D., Q.L. and H.W. collected and analysed the data. D.L. and C.W. provided suggestions and technical support on the project. H.W., K.W. and X.S. performed the theoretical simulations. Z.G.W. and B.D. supervised the project. Z.G.W., B.D., H.W. and Q.L. wrote the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Zhen-Gang Wang, Hui Wang or Baoquan Ding.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–66, Tables 1 and 2, and Discussions 1–4.

Supplementary Video 1

The optical microscopy movie of a self-assembled H15 nanoribbon in MES buffer.

Supplementary Video 2

The optical microscopy movie of a self-assembled H15 nanoribbon in MES buffer.

Supplementary Video 3

The optical microscopy movie of a self-assembled H15 nanopiece in MES buffer.

Supplementary Video 4

The optical microscopy movie of a self-assembled H15 nanosheet in MES buffer.

Crystallographic Data 1

Simulated single-crystal structures of H2 self-assemblies.

Crystallographic Data 2

Simulated single-crystal structures of H15 self-assemblies.

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Liu, Q., Wan, K., Shang, Y. et al. Cofactor-free oxidase-mimetic nanomaterials from self-assembled histidine-rich peptides. Nat. Mater. 20, 395–402 (2021). https://doi.org/10.1038/s41563-020-00856-6

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