Interaction between polysaccharides and toll-like receptor 4: Primary structural role, immune balance perspective, and 3D interaction model hypothesis

Mingzhi Li; Jiajia Wen; Xiaojun Huang; Qixing Nie; Xincheng Wu; Wanning Ma; Shaoping Nie; Mingyong Xie

doi:10.1016/j.foodchem.2021.131586

Interaction between polysaccharides and toll-like receptor 4: Primary structural role, immune balance perspective, and 3D interaction model hypothesis

Food Chem. 2022 Apr 16:374:131586. doi: 10.1016/j.foodchem.2021.131586. Epub 2021 Nov 11.

Authors

Mingzhi Li¹, Jiajia Wen¹, Xiaojun Huang¹, Qixing Nie², Xincheng Wu¹, Wanning Ma¹, Shaoping Nie³, Mingyong Xie⁴

Affiliations

¹ State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
² Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science (Peking University), Ministry of Education, Beijing, China.
³ State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China. Electronic address: spnie@ncu.edu.cn.
⁴ State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China. Electronic address: myxie@ncu.edu.cn.

PMID: 34839969
DOI: 10.1016/j.foodchem.2021.131586

Abstract

Various structural types of polysaccharides are recognized by toll-like receptor 4 (TLR4). However, the mechanism of interaction between the polysaccharides with different structures and TLR4 is unclarified. This review summarized the primary structure of polysaccharides related to TLR4, mainly including molecular weight, monosaccharide composition, glycosidic bonds, functional groups, and branched-chain structure. The optimal primary structure for interacting with TLR4 was obtained by the statistical analysis. Besides, the dual-directional regulation of TLR4 signaling cascade by polysaccharides was also elucidated from an immune balance perspective. Finally, the 3D interaction model of polysaccharides to TLR4-myeloid differentiation factor 2 (MD2) complex was hypothesized according to the LPS-TLR4-MD2 dimerization model and the polysaccharides solution conformation. The essence of polysaccharides binding to TLR4-MD2 complex is a multivalent non-covalent bond interaction. All the arguments summarized in this review are intended to provide some new insights into the interaction between polysaccharides and TLR4.

Keywords: 3D interaction model; Dual-directional regulation; Non-covalent bond; Polysaccharides; Primary structure; Signal cascade; Toll-like receptor 4.

Publication types

Review

MeSH terms

Lipopolysaccharides
Lymphocyte Antigen 96* / metabolism
Polysaccharides
Signal Transduction
Toll-Like Receptor 4* / metabolism

Substances

Lipopolysaccharides
Lymphocyte Antigen 96
Polysaccharides
Toll-Like Receptor 4