TLR 2/1 interaction of pectin depends on its chemical structure and conformation. (1st March 2023)

• Record Type: Journal Article
• Authors: Jermendi, Éva; Fernández-Lainez, Cynthia; Beukema, Martin; López-Velázquez, Gabriel; van den Berg, Marco A.; de Vos, Paul; Schols, Henk A.
• Is Part Of: Carbohydrate polymers. Volume 303(2023)
• Publication Date: 2023-03-01
• Subjects: Citrus pectin -- HILIC-MS -- HPAEC -- Methyl-ester distribution -- Toll-like receptors -- Immunomodulation; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2022.120444
• Languages: English
• ISSNs: 0144-8617

Abstract

Abstract: Citrus pectins have demonstrated health benefits through direct interaction with Toll-like receptor 2. Methyl-ester distribution patterns over the homogalacturonan were found to contribute to such immunomodulatory activity, therefore molecular interactions with TLR2 were studied. Molecular-docking analysis was performed using four GalA-heptamers, GalA7 Me 0, GalA7 Me 1, 6, GalA7 Me 1, 7 and GalA7 Me 2, 5 . The molecular relations were measured in various possible conformations. Furthermore, commercial citrus pectins were characterized by enzymatic fingerprinting using polygalacturonase and pectin-lyase to determine their methyl-ester distribution patterns. The response of 12 structurally different pectic polymers on TLR2 binding and the molecular docking with four pectic oligomers clearly demonstrated interactions with human-TLR2 in a structure-dependent way, where blocks of (non)methyl-esterified GalA were shown to inhibit TLR2/1 dimerization. Our results may be used to understand the immunomodulatory effects of certain pectins via TLR2. Knowledge of how pectins with certain methyl-ester distribution patterns bind to TLRs may lead to tailored pectins to prevent inflammation. Graphical abstract: Unlabelled Image