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Title: Galectins in Host–Pathogen Interactions: Structural, Functional and Evolutionary Aspects
Galectins are a family of ß-galactoside-binding lectins characterized by a unique sequence motif in the carbohydrate recognition domain, and evolutionary and structural conservation from fungi to invertebrates and vertebrates, including mammals. Their biological roles, initially understood as limited to recognition of endogenous (“self”) carbohydrate ligands in embryogenesis and early development, dramatically expanded in later years by the discovery of their roles in tissue repair, cancer, adipogenesis, and regulation of immune homeostasis. In recent years, however, evidence has also accumulated to support the notion that galectins can bind (“non-self”) glycans on the surface of potentially pathogenic microbes, and function as recognition and effector factors in innate immunity. Thus, this evidence has established a newparadigm by which galectins can function not only as pattern recognition receptors but also as effector factors, by binding to the microbial surface and inhibiting adhesion and/or entry into the host cell, directly killing the potential pathogen by disrupting its surface structures, or by promoting phagocytosis, encapsulation, autophagy, and pathogen clearance from circulation. Strikingly, some viruses, bacteria, and protistan parasites take advantage of the aforementioned recognition roles of the vector/host galectins, for successful attachment and invasion. These recent findings suggest that galectin-mediated innate immune recognition and effector mechanisms, which throughout evolution have remained effective for preventing or fighting viral, bacterial, and parasitic infection, have been “subverted” by certain pathogens by unique evolutionary adaptations of their surface glycome to gain host entry, and the acquisition of effective mechanisms to evade the host’s immune responses.  more » « less
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Advances in experimental medicine and biology
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National Science Foundation
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  1. Abstract

    Galectins are soluble carbohydrate binding proteins that can bind β‐galactose‐containing glycoconjugates by means of a conserved carbohydrate recognition domain (CRD). In mammalian systems, galectins have been shown to mediate very important roles in innate and adaptive immunity as well as facilitating host‐pathogen relationships. Many of these studies have relied on purified recombinant galectins to uncover key features of galectin biology. A major limitation to this approach is that certain recombinant galectins purified using standard protocols are easily susceptible to loss of glycan‐binding activity. As a result, biochemical studies that employ recombinant galectins can be misleading if the overall activity of a galectin remains unknown in a given assay condition. This article examines fundamental considerations when purifying galectins by lactosyl‐sepharose and nickel‐NTA affinity chromatography using human galectin‐4N and ‐7 as examples, respectively. As other approaches are also commonly applied to galectin purification, we also discuss alternative strategies to galectin purification, using human galectin‐1 and ‐9 as examples. © 2021 Wiley Periodicals LLC.

    This article was corrected on 20 July 2022. See the end of the full text for details.

    Basic Protocol 1: Purification of galectins using lactosyl‐sepharose affinity chromatography

    Basic Protocol 2: Purification of human galectin‐7 using a nickel‐NTA affinity chromatography column

    Alternate Protocol 1: Iodoacetamide alkylation of free sulfhydryls on galectin‐1

    Alternate Protocol 2: Purification of human galectin‐9 using lactosyl‐sepharose column chromatography

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