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Protein promiscuity and its implications for biotechnology

Nature Biotechnology volume 27, pages 157–167 (2009)Cite this article

Abstract

Molecular recognition between proteins and their interacting partners underlies the biochemistry of living organisms. Specificity in this recognition is thought to be essential, whereas promiscuity is often associated with unwanted side effects, poor catalytic properties and errors in biological function. Recent experimental evidence suggests that promiscuity, not only in interactions but also in the actual function of proteins, is not as rare as was previously thought. This has implications not only for our fundamental understanding of molecular recognition and how protein function has evolved over time but also in the realm of biotechnology. Understanding protein promiscuity is becoming increasingly important not only to optimize protein engineering applications in areas as diverse as synthetic biology and metagenomics but also to lower attrition rates in drug discovery programs, identify drug interaction surfaces less susceptible to escape mutations and potentiate the power of polypharmacology.

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Figure 1
Figure 2: Structural flexibility and promiscuous binding.
Figure 3: The short-chain dehydrogenase/reductase proteins.
Figure 4: Toy schemata illustrating how size and complexity of a protein's interacting partners can affect the chances of an effective binding.

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Acknowledgements

The authors thank David Moss for his suggestions for improving the manuscript.

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  1. Institute of Structural and Molecular Biology, School of Crystallography, Birkbeck, University of London, Malet Street, London, WC1E 7HX, UK

    Irene Nobeli

  2. EMBL Outstation–Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SD, Cambridge, UK

    Angelo D Favia & Janet M Thornton

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Nobeli, I., Favia, A. & Thornton, J. Protein promiscuity and its implications for biotechnology. Nat Biotechnol 27, 157–167 (2009). https://doi.org/10.1038/nbt1519

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  • DOI: https://doi.org/10.1038/nbt1519

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