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Implications of molecular heterogeneity for the cooperativity of biological macromolecules

Nature Structural & Molecular Biology volume 18, pages 732–734 (2011)Cite this article

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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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Figure 1: Simulations of ligand binding cooperativity with a heterogeneous population of molecules.
Figure 2: smFRET measurements of P4-P6 RNA folding.
Figure 3: Cooperativity of Ba2+-dependent folding for 126 P4-P6 molecules measured by smFRET.

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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.

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Author notes

  1. Sergey V Solomatin and Max Greenfeld: These authors contributed equally to this work.

Authors and 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

Authors
  1. Sergey V Solomatin
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  2. Max Greenfeld
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  3. Daniel Herschlag
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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.

Corresponding author

Correspondence to Daniel Herschlag.

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The authors declare no competing financial interests.

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Supplementary Figures 1–3, Supplementary Methods and Supplementary Note (PDF 286 kb)

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Solomatin, S., Greenfeld, M. & Herschlag, D. Implications of molecular heterogeneity for the cooperativity of biological macromolecules. Nat Struct Mol Biol 18, 732–734 (2011). https://doi.org/10.1038/nsmb.2052

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