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Mechanism of Mucin Recognition by Lectins: A Thermodynamic Study

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Galectins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2442))

Abstract

Isothermal titration microcalorimetry (ITC) can directly determine the thermodynamic binding parameters of biological molecules including affinity constant, binding stoichiometry, heat of binding (enthalpy) and indirectly the entropy, and free energy of binding. ITC has been extensively used to study the binding of lectins to mono- and oligosaccharides, but limitedly in applications to lectin–glycoprotein interactions. Inherent experimental challenges to ITC include sample precipitation during the experiment and relative high amount of sample required, but careful design of experiments can minimize these problems and allow valuable information to be obtained. For example, the thermodynamics of binding of lectins to multivalent globular and linear glycoproteins (mucins) have been described. The results are consistent with a dynamic binding mechanism in which lectins bind and jump from carbohydrate to carbohydrate epitope in these molecules leading to increased affinity. Importantly, the mechanism of binding of lectins to mucins appears similar to that for a variety of protein ligands binding to DNA. Recent results also show that high-affinity lectin–mucin cross-linking interactions are driven by favorable entropy of binding that is associated with the bind and jump mechanism. The results suggest that the binding of ligands to biopolymers, in general, may involve a common mechanism that involves enhanced entropic effects that facilitate binding interactions.

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Acknowledgments

Part of this work was supported by National Science Foundation Grant 1608537 (to T.K.D.). A part of this work was supported by a startup fund (to P.B.) and by the Research Excellence Fund (to T.K.D.) provided by Michigan Technological University.

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Authors and Affiliations

  1. Laboratory of Mechanistic Glycobiology Department of Chemistry, Michigan Technological University, Houghton, MI, USA

    Tarun K. Dam, Jared L. Edwards & Priyanka D. Kadav

  2. Health Research Institute, Michigan Technological University, Houghton, MI, USA

    Tarun K. Dam

  3. Departments of Molecular Pharmacology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA

    C. Fred Brewer

Authors
  1. Tarun K. Dam
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  2. Jared L. Edwards
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  3. Priyanka D. Kadav
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  4. C. Fred Brewer
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Corresponding author

Correspondence to Tarun K. Dam .

Editor information

Editors and Affiliations

  1. Joint Program in Transfusion Medicine Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Sean R. Stowell

  2. Joint Program in Transfusion Medicine Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Connie M. Arthur

  3. Department of Surgery Beth Israel Deaconess Medical Center National Center for Functional Glycomics, Harvard Medical School, Boston, MA, USA

    Richard D. Cummings

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Dam, T.K., Edwards, J.L., Kadav, P.D., Brewer, C.F. (2022). Mechanism of Mucin Recognition by Lectins: A Thermodynamic Study. In: Stowell, S.R., Arthur, C.M., Cummings, R.D. (eds) Galectins. Methods in Molecular Biology, vol 2442. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2055-7_10

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  • DOI: https://doi.org/10.1007/978-1-0716-2055-7_10

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2054-0

  • Online ISBN: 978-1-0716-2055-7

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