Structural analysis of carbohydrate binding by the macrophage mannose receptor CD206.
Structural analysis of carbohydrate binding by the macrophage mannose receptor CD206.
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DOI：
10.1016/j.jbc.2021.100368
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Taylor ME
中科院分区：
文献类型：
--
作者：
Feinberg H;Jégouzo SAF;Lasanajak Y;Smith DF;Drickamer K;Weis WI;Taylor ME
在巨噬细胞和肝内皮细胞上表达的人甘露糖受体清除释放的溶酶体酶、胶原蛋白的糖肽片段和病原微生物，从而减少组织损伤后的损伤。受体结合这些靶标上的甘露糖、岩藻糖或N-乙酰葡糖胺（GlcNAc）残基。受体的C型碳水化合物识别结构域4（CRD 4）包含与糖的Ca 2+依赖性相互作用的位点。为了研究CRD 4结合的细节，使用聚糖阵列筛选来鉴定寡糖配体。最强的信号是含有Manα1- 2 Man成分或各种键中的岩藻糖的聚糖。在CRD 4的多个晶体结构中检查了与许多这些配体中存在的单糖和寡糖亚结构结合的机制。甘露糖残基与CRD 4的结合主要是由于赤道3-和4-OH基团与几乎所有糖结合C型CRD共有的保守的主要Ca 2+的相互作用。在Manα1- 2 Man复合物中，与还原性甘露糖残基的补充相互作用解释了对该二糖的亲和力增强。结合的GlcNAc也通过赤道3-和4-OH基团与主要的Ca 2+相互作用，而岩藻糖残基可以通过2-和3-OH基团或3-和4-OH基团以几个方向结合。与含岩藻糖寡糖中的其他糖（如路易斯-α三糖）的二级接触可增强对这些聚糖的亲和力。这些结果解释了甘露糖受体与哺乳动物糖蛋白和微生物如酵母的许多生物学上重要的相互作用，并提出了先前未鉴定的其他配体类别。
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.
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DOI：
10.1074/jbc.m117.799080
发表时间：
2017-08-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Feinberg H;Jégouzo SAF;Rex MJ;Drickamer K;Weis WI;Taylor ME
通讯作者：
Taylor ME
影响因子：
4.8
作者：
East, L;Rushton, S;Isacke, CM
通讯作者：
Isacke, CM
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.8
作者：
Feinberg, H;Park-Snyder, S;Weis, WI
通讯作者：
Weis, WI
DOI：
10.1073/pnas.94.21.11256
发表时间：
1997-10-14
影响因子：
11.1
作者：
Fiete, D;Beranek, MC;Baenziger, JU
通讯作者：
Baenziger, JU