Structure of a C-type carbohydrate recognition domain from the macrophage mannose receptor
Structure of a C-type carbohydrate recognition domain from the macrophage mannose receptor
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DOI：
10.1074/jbc.m002366200
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发表时间：
2000-07-14
影响因子：
4.8
通讯作者：
Weis, WI
中科院分区：
文献类型：
--
作者：
Feinberg, H;Park-Snyder, S;Weis, WI
巨噬细胞和肝内皮的甘露糖受体介导病原微生物和潜在有害糖复合物的清除。该受体的胞外部分包括8个C型碳水化合物识别结构域（CRD），其中一个CRD-4显示出可检测到的与单糖配体的结合，我们已经确定了CRD-4的晶体结构，虽然基本的C型凝集素折叠被保留，但环从结构域的核心延伸出来，在晶体中形成结构域交换的二聚体。在两个 Ca2+ 位点中，只有已知介导其他 C 型凝集素中碳水化合物结合的主要位点被占据。该位点的改变方式使得糖结合不可能以其他 C 型凝集素中观察到的模式进行。该结构可能代表当 Ca2+ 从辅助钙位点丢失时形成的结构域的内体形式。该结构表明了一种内体配体释放的机制，其中辅助钙位点充当 pH 传感器。酸性 pH 诱导的 Ca2+ 去除会导致受体构象重排，使其无法结合碳水化合物配体。
The mannose receptor of macrophages and liver endothelium mediates clearance of pathogenic organisms and potentially harmful glycoconjugates. The extracellular portion of the receptor includes eight C-type carbohydrate recognition domains (CRDs), of which one, CRD-4, shows detectable binding to monosaccharide ligands, We have determined the crystal structure of CRD-4, Although the basic C-type lectin fold is preserved, a loop extends away from the core of the domain to form a domain-swapped dimer in the crystal. Of the two Ca2+ sites, only the principal site known to mediate carbohydrate binding in other C-type lectins is occupied. This site is altered in a way that makes sugar binding impossible in the mode observed in other C-type lectins, The structure is likely to represent an endosomal form of the domain formed when Ca2+ is lost from the auxiliary calcium site, The structure suggests a mechanism for endosomal ligand release in which the auxiliary calcium site serves as a pH sensor. Acid pH-induced removal of this Ca2+ results in conformational rearrangements of the receptor, rendering it unable to bind carbohydrate ligands.