Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain
Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain
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DOI：
10.1093/emboj/19.4.504
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发表时间：
2000-02-15
期刊：
影响因子：
11.4
通讯作者：
Muller, YA
中科院分区：
文献类型：
--
作者：
Grishkovskaya, I;Avvakumov, GV;Muller, YA
人类性激素结合球蛋白（SHBG）在血液中运输性类固醇并调节其进入靶组织。在生物流体中，SHBG以同二聚体的形式存在，每个单体包含两个层粘连蛋白G样结构域（G结构域）。在1.55埃的分辨率下，SHBG与5 α -二氢睾酮配合物的n端G结构域的晶体结构揭示了甾体结合位点的结构和二聚体的四元结构，我们还发现G结构域具有果冻状拓扑结构，并且在结构上与戊烷素相关。在每个SHBG单体中，类固醇嵌入到β -薄片夹层中的疏水口袋中。甾体和一个20埃远钙离子不在二聚体界面上。相反，每个二聚体存在两个独立的类固醇结合口袋和钙结合位点，环段Pro130-Arg135的结构显示出有趣的紊乱。在所有其他水母蛋白中，这个循环是有序的。如果建立相应的模型，它覆盖了类固醇结合位点，从而可以调节配体进入结合袋。
Human sex hormone-binding globulin (SHBG) transports sex steroids in blood and regulates their access to target tissues. In biological fluids, SHBG exists as a homodimer and each monomer comprises two laminin G-like domains (G domains). The crystal structure of the N-terminal G domain of SHBG in complex with 5 alpha-dihydrotestosterone at 1.55 Angstrom resolution reveals both the architecture of the steroid-binding site and the quaternary structure of the dimer, We also show that G domains have jellyroll topology and are structurally related to pentraxin. In each SHBG monomer, the steroid intercalates into a hydrophobic pocket within the beta-sheet sandwich. The steroid and a 20 Angstrom distant calcium ion are not located at the dimer interface. Instead, two separate steroid-binding pockets and calcium-binding sites exist per dimer, The structure displays intriguing disorder for loop segment Pro130-Arg135. In all other jellyroll proteins, this loop is well ordered. If modelled accordingly, it covers the steroid-binding site and could thereby regulate access of ligands to the binding pocket.