Brief Communication | Published:

Implications of molecular heterogeneity for the cooperativity of biological macromolecules

Nature Structural & Molecular Biology volume 18, pages 732734 (2011) | Download Citation

Abstract

Cooperativity, a universal property of biological macromolecules, is typically characterized by a Hill slope, which can provide fundamental information about binding sites and interactions. We demonstrate, through simulations and single-molecule FRET (smFRET) experiments, that molecular heterogeneity lowers bulk cooperativity from the intrinsic value for the individual molecules. As heterogeneity is common in smFRET experiments, appreciation of its influence on fundamental measures of cooperativity is critical for deriving accurate molecular models.

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Acknowledgements

We thank H. Mabuchi (Department of Applied Physics, Stanford University) for technical support and D. Pavlichin for helping to create data analysis software. This work was funded by the US National Institutes of Health through grant GM49243 to D.H.

Author information

Author notes

    • Sergey V Solomatin
    •  & Max Greenfeld

    These authors contributed equally to this work.

Affiliations

  1. Department of Biochemistry, Stanford University, Stanford, California, USA.

    • Sergey V Solomatin
    • , Max Greenfeld
    •  & Daniel Herschlag
  2. Department of Chemical Engineering, Stanford University, Stanford, California, USA.

    • Max Greenfeld

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Contributions

S.V.S., M.G. and D.H. contributed to the experimental design and writing of the manuscript; M.G. performed the experiments; and M.G. and S.V.S. carried out data analysis.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Daniel Herschlag.

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DOI

https://doi.org/10.1038/nsmb.2052

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