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首页> 外文期刊>Journal of Molecular Biology >EXTENDED GLYCOPROTEIN STRUCTURE OF THE SEVEN DOMAINS IN HUMAN CARCINOEMBRYONIC ANTIGEN BY X-RAY AND NEUTRON SOLUTION SCATTERING AND AN AUTOMATED CURVE FITTING PROCEDURE - IMPLICATIONS FOR CELLULAR ADHESION
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EXTENDED GLYCOPROTEIN STRUCTURE OF THE SEVEN DOMAINS IN HUMAN CARCINOEMBRYONIC ANTIGEN BY X-RAY AND NEUTRON SOLUTION SCATTERING AND AN AUTOMATED CURVE FITTING PROCEDURE - IMPLICATIONS FOR CELLULAR ADHESION

机译:X射线和中子溶液散射和自动曲线拟合程序扩展了人类癌胚神经抗原中七个区域的糖蛋白结构-对细胞粘附的意义

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Carcinoembryonic antigen (CEA) is one of the most widely used cell-surface tumour markers for tumour monitoring and for targeting by antibodies. It is heavily glycosylated (50% carbohydrate) and a monomer is constructed from one V-type and six C2-type fold domains of the immunoglobulin superfamily. The solution arrangement at low resolution of the seven domains in CEA cleaved from its membrane anchor was determined by X-ray and neutron scattering. Guinier analyses showed that the X-ray radius of gyration R(G) Of CEA was 8.0 nm. The length of CEA was 27 to 33 nm, and is consistent with an extended arrangement of seven domains. The X-ray cross-sectional radius of gyration R(xs) was 2.1 nm, and is consistent with extended carbohydrate structures in CEA. The neutron data gave CEA a relative molecular mass of 150,000, in agreement with a value of 152,500 from composition data, and validated the X-ray analyses. The CEA scattering curves were analysed using an automated computer modelling procedure based on the crystal structure of CD2. The V-type and C2-type domains in CD2 were separated, and the C2-type domain was duplicated five times to create a linear seven-domain starting model for CEA. A total of 28 complex-type oligosaccharide chains in extended conformations were added to this model. By fixing the six interdomain orientations to be the same, three-parameter searches of the rotational orientations between the seven domains gave 4056 possible CEA models. The best curve fits from these corresponded to a family of zig-zag models. The long axis of each domain was set at 160(+/-25)degrees relative to its neighbour, and the two perpendicular axes were orientated at 10(+/-30)degrees and -5(+/-35)degrees. Interestingly, the curve fit from this model is within error of that calculated from a CEA model generated directly from the CD2 crystal structure by the superposition of adjacent domains. Zig-zag models of this type imply that the protein face of the GFCC' beta-sheet in neighbouring CEA domains lie on alternate sides of the CEA structure. Such a model has implications for the adhesion interactions between CEA molecules on adjacent cells or for the antibody targeting of CEA. (C) 1996 Academic Press Limited [References: 73]
机译:癌胚抗原(CEA)是用于肿瘤监测和抗体靶向的最广泛使用的细胞表面肿瘤标志物之一。它被高度糖基化(50%的碳水化合物),并且单体是由免疫球蛋白超家族的一个V型和六个C2型折叠域构成的。通过X射线和中子散射确定从其膜锚分离的CEA中七个域的低分辨率溶液排列。 Guinier分析表明,CEA的X射线旋转半径R(G)为8.0 nm。 CEA的长度为27至33nm,并且与七个结构域的扩展排列一致。回转的X射线横截面半径R(xs)为2.1 nm,与CEA中扩展的碳水化合物结构一致。中子数据给出了CEA的相对分子质量150,000,与成分数据的152,500一致,并验证了X射线分析。使用自动计算机建模程序基于CD2的晶体结构分析CEA散射曲线。分离CD2中的V型和C2型结构域,并将C2型结构域重复五次以创建CEA的线性七域起始模型。总共28个扩展构象的复合型寡糖链被添加到该模型中。通过将六个域间方向固定为相同,对七个域之间的旋转方向进行三参数搜索可获得4056种可能的CEA模型。这些中的最佳曲线拟合对应于一个之字形模型系列。每个域的长轴相对于其邻居设置为160(+/- 25)度,两个垂直轴的方向分别为10(+/- 30)度和-5(+/- 35)度。有趣的是,该模型的曲线拟合在由CEA模型计算得出的误差范围之内,该CEA模型是通过相邻域的叠加直接从CD2晶体结构生成的。此类型的Zig-zag模型暗示,在相邻CEA域中GFCC'β-sheet的蛋白面位于CEA结构的另一侧。这种模型对相邻细胞上CEA分子之间的粘附相互作用或对CEA的抗体靶向具有影响。 (C)1996 Academic Press Limited [参考号:73]

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