Rudenko Gabby, Henry Lisa, Henderson Keith, Ichtchenko Konstantin, Brown Michael S, Goldstein Joseph L, Deisenhofer Johann
Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard Y4-206, Dallas, TX 75390, USA.
Science. 2002 Dec 20;298(5602):2353-8. doi: 10.1126/science.1078124. Epub 2002 Nov 29.
The low-density lipoprotein receptor mediates cholesterol homeostasis through endocytosis of lipoproteins. It discharges its ligand in the endosome at pH < 6. In the crystal structure at pH = 5.3, the ligand-binding domain (modules R2 to R7) folds back as an arc over the epidermal growth factor precursor homology domain (the modules A, B, beta propeller, and C). The modules R4 and R5, which are critical for lipoprotein binding, associate with the beta propeller via their calcium-binding loop. We propose a mechanism for lipoprotein release in the endosome whereby the beta propeller functions as an alternate substrate for the ligand-binding domain, binding in a calcium-dependent way and promoting lipoprotein release.
低密度脂蛋白受体通过脂蛋白的内吞作用介导胆固醇稳态。它在pH < 6的内体中释放其配体。在pH = 5.3的晶体结构中，配体结合结构域（模块R2至R7）作为一个弧形折叠在表皮生长因子前体同源结构域（模块A、B、β螺旋桨和C）之上。对脂蛋白结合至关重要的模块R4和R5通过其钙结合环与β螺旋桨结合。我们提出了一种在内体中释放脂蛋白的机制，即β螺旋桨作为配体结合结构域的替代底物，以钙依赖的方式结合并促进脂蛋白释放。
