TRIMERIC STRUCTURE OF A C-TYPE MANNOSE-BINDING PROTEIN
TRIMERIC STRUCTURE OF A C-TYPE MANNOSE-BINDING PROTEIN
复制标题
DOI：
10.1016/s0969-2126(94)00124-3
复制
发表时间：
1994-12-15
期刊：
影响因子：
5.7
通讯作者：
DRICKAMER, K
中科院分区：
文献类型：
--
作者：
WEIS, WI;DRICKAMER, K
背景：甘露糖结合蛋白(MBP)是存在于血清中的C型(钙依赖)动物凝集素。它们识别病原菌和真菌特有的细胞表面低聚糖结构，并触发这些生物的中和。与大多数凝集素一样，MBPS对单价糖配体的内在亲和力很弱，但与多价配体的亲和力很强。结果：我们报道了MBP-A三聚体片段在溶液中的物理研究和晶体结构，该片段包含碳水化合物识别结构域(CRD)和将CRD的羧基末端连接到完整分子的胶原样部分的颈区，布拉格间距为1.8埃。颈部由一个平行的三链螺旋组成，由四个残基连接到CRD上。分离的Neck多肽不能形成稳定的形式。水溶液中的螺旋。结论：MBP-A中的糖结合位点距离太远，单个三聚体不能与典型的哺乳动物高甘露糖低聚糖多价结合。因此，MBPS可以通过与病原体细胞表面广泛分布的、重复的糖链结合来选择性地识别病原体。序列比对表明，其他C型凝集素可能具有类似的寡聚体结构，但它们详细组织的差异将在确定它们与寡糖的相互作用方面发挥重要作用。
Background: Mannose-binding proteins (MBPs) are C-type (Ca2+-dependent) animal lectins found in serum. They recognize cell-surface oligosaccharide structures characteristic of pathogenic bacteria and fungi, and trigger the neutralization of these organisms. Like most lectins, MBPs display weak intrinsic affinity for monovalent sugar ligands, but bind avidly to multivalent ligands.Results: We report physical studies in solution and the crystal structure determined at 1.8 Angstrom Bragg spacings of a trimeric fragment of MBP-A, containing the carbohydrate-recognition domain (CRD) and the neck domain that links the carboxy-terminal CRD to the collagen-like portion of the intact molecule. The neck consists of a parallel triple-stranded coiled coil of alpha-helices linked by four residues to the CRD. The isolated neck peptide does not form stable. helices in aqueous solution. The previously characterized carbohydrate-binding sites lie at the distal end of the trimer and are separated from each other by 53 Angstrom.Conclusions: The carbohydrate-binding sites in MBP-A are too far apart for a single trimer to bind multivalently to a typical mammalian high-mannose oligosaccharide. Thus MBPs can recognize pathogens selectively by binding avidly only to the widely spaced, repetitive sugar arrays on pathogenic cell surfaces. Sequence alignments reveal that other C-type lectins are likely to have a similar oligomeric structure, but differences in their detailed organization will have an important role in determining their interactions with oligosaccharides.