Structural Insights into the pH-Dependent Conformational Change and Collagen Recognition of the Human Mannose Receptor

Zhenzheng Hu; Xiangyi Shi; Bowen Yu; Na Li; Ying Huang; Yongning He

doi:10.1016/j.str.2017.11.006

Structural Insights into the pH-Dependent Conformational Change and Collagen Recognition of the Human Mannose Receptor

Structure. 2018 Jan 2;26(1):60-71.e3. doi: 10.1016/j.str.2017.11.006. Epub 2017 Dec 7.

Authors

Zhenzheng Hu¹, Xiangyi Shi¹, Bowen Yu¹, Na Li¹, Ying Huang¹, Yongning He²

Affiliations

¹ State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Shanghai Science Research Center, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 333 Haike Road, Shanghai 201210, China.
² State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Shanghai Science Research Center, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 333 Haike Road, Shanghai 201210, China. Electronic address: he@sibcb.ac.cn.

PMID: 29225077
DOI: 10.1016/j.str.2017.11.006

Abstract

Mannose receptor (MR, CD206) is an endocytic receptor on microphages and dendritic cells. It recognizes multiple ligands and plays important roles in regulating immune responses and maintaining glycoprotein homeostasis. However, the structure and functional mechanism of MR remain unclear. Here we determine the crystal structures of the N-terminal fragments of MR and reveal the potential binding mode of collagen on the fibronectin II domain. The SAXS and other biophysical data suggest that MR adopts an extended conformation at physiological pH and undergoes conformational changes as pH decreases, resulting in a compact conformation in an acidic environment. Moreover, biochemical data show that MR binds to collagen in a Ca²⁺-enhanced manner at physiological pH, whereas Ca²⁺ has no effect on the binding at acidic pH. These results provide a model for the dynamic mechanism of MR regarding its ligand binding and release during the recycling between cell surface and endosomes.

Keywords: CD206; collagen; conformational change; immune receptor; mannose receptor; mannose receptor family.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Baculoviridae / genetics
Baculoviridae / metabolism
Binding Sites
Calcium / chemistry*
Calcium / metabolism
Cations, Divalent
Cloning, Molecular
Collagen Type I / chemistry*
Collagen Type I / genetics
Collagen Type I / metabolism
Crystallography, X-Ray
Fibronectins / chemistry*
Fibronectins / genetics
Fibronectins / metabolism
Gene Expression
Genetic Vectors / chemistry
Genetic Vectors / metabolism
HEK293 Cells
Humans
Hydrogen-Ion Concentration
Lectins, C-Type / chemistry*
Lectins, C-Type / genetics
Lectins, C-Type / metabolism
Ligands
Mannose Receptor
Mannose-Binding Lectins / chemistry*
Mannose-Binding Lectins / genetics
Mannose-Binding Lectins / metabolism
Models, Molecular
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Rats
Receptors, Cell Surface / chemistry*
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Sf9 Cells
Spodoptera

Substances

Cations, Divalent
Collagen Type I
Fibronectins
Lectins, C-Type
Ligands
Mannose Receptor
Mannose-Binding Lectins
Receptors, Cell Surface
Recombinant Proteins
Calcium