Mechanism of Mucin Recognition by Lectins: A Thermodynamic Study

Tarun K. Dam, Jared L. Edwards, Priyanka D. Kadav, C. Fred Brewer

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages169-185
Number of pages17
DOIs
StatePublished - 2022

Publication series

NameMethods in Molecular Biology
Volume2442
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Bind and jump model
  • Entropy
  • Glycoproteins
  • Internal diffusion
  • Lectins
  • Mucins
  • Multivalent carbohydrates
  • Thermodynamics

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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