Abstract
Proteins represent the most sophisticated building blocks available to an organism and to the laboratory chemist. Yet, in contrast to nearly all other types of molecular building blocks, the designed self-assembly of proteins has largely been inaccessible because of the chemical and structural heterogeneity of protein surfaces. To circumvent the challenge of programming extensive non-covalent interactions to control protein self-assembly, we have previously exploited the directionality and strength of metal coordination interactions to guide the formation of closed, homoligomeric protein assemblies. Here, we extend this strategy to the generation of periodic protein arrays. We show that a monomeric protein with properly oriented coordination motifs on its surface can arrange, on metal binding, into one-dimensional nanotubes and two- or three-dimensional crystalline arrays with dimensions that collectively span nearly the entire nano- and micrometre scale. The assembly of these arrays is tuned predictably by external stimuli, such as metal concentration and pH.
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Acknowledgements
This work was primarily supported by the US Department of Energy (DOE) (Division of Materials Sciences, Office of Basic Energy Sciences, Award DE-FG02-10ER46677 to F.A.T.). Additional support was provided by the Agouron Foundation, Beckman Foundation, Sloan Foundation, National Science Foundation (CHE-0908115 to F.A.T., protein design), National Institutes of Health (EM characterization, R37GM-033050 and 1S10 RR.020016 to T.S.B. and F32 AI078624 to K.N.P.) and the University of California, San Diego. Portions of this research were carried out at Stanford Synchrotron Radiation Lightsource, operated by Stanford University on behalf of the DOE.
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J.D.B. designed and performed most of the experiments and data analysis, and co-wrote the paper. X.I.A. performed computational interface design calculations. C.T. and K.N.P. provided guidance and assistance with EM data collection and analysis. T.S.B. guided EM data analysis and co-wrote the paper. F.A.T. initiated and directed the project, analysed data and co-wrote the paper.
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Brodin, J., Ambroggio, X., Tang, C. et al. Metal-directed, chemically tunable assembly of one-, two- and three-dimensional crystalline protein arrays. Nature Chem 4, 375–382 (2012). https://doi.org/10.1038/nchem.1290
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DOI: https://doi.org/10.1038/nchem.1290
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