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Structural analysis of carbohydrate binding by the macrophage mannose receptor CD206

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Title: Structural analysis of carbohydrate binding by the macrophage mannose receptor CD206
Authors: Feinberg, H
Jégouzo, SAF
Lasanajak, Y
Smith, DF
Drickamer, K
Weis, WI
Taylor, ME
Item Type: Journal Article
Abstract: The human mannose receptor expressed on macrophages and hepatic endothelial cells scavenges released lysosomal enzymes, glycopeptide fragments of collagen, and pathogenic microorganisms and thus reduces damage following tissue injury. The receptor binds mannose, fucose, or N-acetylglucosamine (GlcNAc) residues on these targets. C-type carbohydrate-recognition domain 4 (CRD4) of the receptor contains the site for Ca2+-dependent interaction with sugars. To investigate the details of CRD4 binding, glycan array screening was used to identify oligosaccharide ligands. The strongest signals were for glycans that contain either Manα1-2Man constituents or fucose in various linkages. The mechanisms of binding to monosaccharides and oligosaccharide substructures present in many of these ligands were examined in multiple crystal structures of CRD4. Binding of mannose residues to CRD4 results primarily from interaction of the equatorial 3- and 4-OH groups with a conserved principal Ca2+ common to almost all sugar-binding C-type CRDs. In the Manα1-2Man complex, supplementary interactions with the reducing mannose residue explain the enhanced affinity for this disaccharide. Bound GlcNAc also interacts with the principal Ca2+ through equatorial 3- and 4-OH groups, whereas fucose residues can bind in several orientations, through either the 2- and 3-OH groups or the 3- and 4-OH groups. Secondary contacts with additional sugars in fucose-containing oligosaccharides, such as the Lewis-a trisaccharide, provide enhanced affinity for these glycans. These results explain many of the biologically important interactions of the mannose receptor with both mammalian glycoproteins and microbes such as yeast and suggest additional classes of ligands that have not been previously identified.
Issue Date: Feb-2021
Date of Acceptance: 1-Feb-2021
URI: http://hdl.handle.net/10044/1/86922
DOI: 10.1016/j.jbc.2021.100368
ISSN: 0021-9258
Publisher: Elsevier BV
Start Page: 1
End Page: 18
Journal / Book Title: Journal of Biological Chemistry
Volume: 296
Copyright Statement: © 2021 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CCBY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: BB/P005659/1
Keywords: C-type lectin
carbohydrate-binding protein
crystal structure
scavenger receptor
Biochemistry & Molecular Biology
03 Chemical Sciences
06 Biological Sciences
11 Medical and Health Sciences
Publication Status: Published
Open Access location: https://doi.org/10.1016/j.jbc.2021.100368
Article Number: 100368
Online Publication Date: 2021-02-02
Appears in Collections:Faculty of Natural Sciences

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