Department of Neurology, Glostrup Research Institute, Glostrup, Denmark.
Institute of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Prog Mol Subcell Biol. 2021;59:13-25. doi: 10.1007/978-3-030-67696-4_2.
Calreticulin (Calr) is an endoplasmic reticulum (ER) chaperone involved in protein quality control, Ca regulation and other cellular processes. The structure of Calr is unusual, reflecting different functions of the protein: a proline-rich β-hairpin arm and an acidic C-terminal tail protrude from a globular core, composed of a β-sheet sandwich and an α-helix. The arm and tail interact in the presence of Ca and cover the upper β-sheet, where a carbohydrate-binding site gives the chaperone glycoprotein affinity. At the edge of the carbohydrate-binding site is a conserved, strained disulphide bridge, formed between C and C of human Calr, which lies in a polypeptide-binding site. The lower β-sheet has several conserved residues, comprised of a characteristic triad, D-H-D, Tyr and the free C. In addition to its role in the ER, Calr translocates to the cell surface upon stress and functions as an immune surveillance marker. In some myeloproliferative neoplasms, the acidic Ca-binding C-terminal tail is transformed into a polybasic sequence.
钙网织蛋白（Calreticulin，Calr）是内质网（Endoplasmic reticulum，ER）伴侣蛋白，参与蛋白质质量控制、Ca 调节和其他细胞过程。Calr 的结构很不寻常，反映了该蛋白的不同功能：富含脯氨酸的 β 发夹臂和酸性 C 端尾巴从由β-折叠夹心和α-螺旋组成的球状核心中伸出。在 Ca 的存在下，臂和尾巴相互作用，并覆盖在上层β-折叠上，其中碳水化合物结合位点赋予伴侣糖蛋白亲和力。在碳水化合物结合位点的边缘是一个保守的、应变的二硫键，由人 Calr 的 C 和 C 形成，位于多肽结合位点。较低的β-折叠有几个保守残基，由一个特征三联体、D-H-D、Tyr 和游离 C 组成。除了在 ER 中的作用外，Calr 在应激时易位到细胞表面，并作为免疫监测标记发挥作用。在一些骨髓增生性肿瘤中，酸性的 Ca 结合 C 端尾巴转化为多碱性序列。
