Assignment of disulphide bonds in human platelet GPIIIa. A disulphide pattern for the beta-subunits of the integrin family.
Assignment of disulphide bonds in human platelet GPIIIa. A disulphide pattern for the beta-subunits of the integrin family.
复制标题
人血小板 GPIIIa 中二硫键的分配。
作者：
J. Calvete;Agnes HENSCHENt;J. González
整联蛋白是由一个α亚基和一个β亚基结合形成的细胞表面异二聚体。糖蛋白 IIIa（GPIIIa 或 β 3 亚基）是整联蛋白 β 3 亚家族的常见 β 亚基，当与糖蛋白 IIb (GPIIb) 结合时，构成血小板表面纤维蛋白原和其他粘附蛋白（GPIIb-IIIa 复合物）的受体，当与 α v 亚基结合时，构成存在于多种细胞类型中的玻连蛋白受体。 GPIIIa 的蛋白质化学分析使我们能够定义以下结构域：富含半胱氨酸且耐蛋白酶的 N 末端结构域 (GPIIIa 1-62)；粘附蛋白结合结构域（GPIIIa 101-422）；富含半胱氨酸且耐蛋白酶的核心（GPIIIa 423-622）； [0132] C末端结构域包含胞外亚结构域（GPIIIa 623-692)、跨膜亚结构域（GPIIIa 693-721)和细胞质亚结构域（GPIIIa 722-762)。我们还明确指定了 N 端、纤维蛋白原结合结构域和 C 端结构域内的二硫键，以及将 N 端连接到蛋白酶抗性核心 (Cys5-Cys435) 和将纤维蛋白原结合结构域连接到 C 端结构域 (Cys406-Cys655) 胞外侧的两个长程二硫键。此外，我们提出了三种替代模型来排列核心内的二硫键以及将核心连接到C末端结构域的细胞外侧的二硫键，这与我们的实验结果一致，暂时倾向于对这些二硫键的形成施加较少的空间障碍。基于这些信息以及迄今为止在已知的整联蛋白家族的β亚基中观察到的高度保守的整体结构（β4除外），我们建议将此处概述的GPIIIa的半胱氨酸配对模式和结构域扩展到整联蛋白家族的所有β亚基。
Integrins are cell-surface heterodimers formed by the association of one alpha- and one beta-subunit. Glycoprotein IIIa (GPIIIa or beta 3 subunit) is the common beta-subunit of the beta 3 subfamily of integrins, which, when associated with glycoprotein IIb (GPIIb), constitutes the receptor for fibrinogen and other adhesive proteins at the platelet surface (the GPIIb-IIIa complex) and, when associated with the alpha v-subunit, constitutes the vitronectin receptor present in several cell types. Protein chemical analysis of GPIIIa allows us to define the following structural domains: the cysteine-rich and proteinase-resistant N-terminal domain (GPIIIa 1-62); the adhesive-protein-binding domain (GPIIIa 101-422); the cysteine-rich and proteinase-resistant core (GPIIIa 423-622); and the C-terminal domain comprising an extracellular subdomain (GPIIIa 623-692), a transmembrane subdomain (GPIIIa 693-721), and a cytoplasmic subdomain (GPIIIa 722-762). We also assign unambiguously the disulphide bonds within the N-terminal, the fibrinogen-binding and the C-terminal domains, and the two long-range disulphide bonds which join the N-terminus to the proteinase-resistant core (Cys5-Cys435) and the fibrinogen-binding domain to the extracellular side of the C-terminal domain (Cys406-Cys655). In addition, we propose three alternative models for the arrangement of the disulphide bonds within the core and of the disulphide bonds joining the core to the extracellular side of the C-terminal domain, consistent with our experimental findings, favouring temporarily that which imposes less steric hindrance for the formation of these disulphide bonds. On the basis of this information and on the highly conserved overall structure observed in the beta-subunits of the integrin family known so far, except in beta 4, we propose to extend the cysteine-pairing pattern and the structural domains outlined here for GPIIIa to all the beta-subunits of the integrin family.