Ren Xuefeng, Kloer Daniel P, Kim Young C, Ghirlando Rodolfo, Saidi Layla F, Hummer Gerhard, Hurley James H
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
Structure. 2009 Mar 11;17(3):406-16. doi: 10.1016/j.str.2009.01.012.
The human Hrs and STAM proteins comprise the ESCRT-0 complex, which sorts ubiquitinated cell surface receptors to lysosomes for degradation. Here we report a model for the complete ESCRT-0 complex based on the crystal structure of the Hrs-STAM core complex, previously solved domain structures, hydrodynamic measurements, and Monte Carlo simulations. ESCRT-0 expressed in insect cells has a hydrodynamic radius of RH = 7.9 nm and is a 1:1 heterodimer. The 2.3 Angstroms crystal structure of the ESCRT-0 core complex reveals two domain-swapped GAT domains and an antiparallel two-stranded coiled-coil, similar to yeast ESCRT-0. ESCRT-0 typifies a class of biomolecular assemblies that combine structured and unstructured elements, and have dynamic and open conformations to ensure versatility in target recognition. Coarse-grained Monte Carlo simulations constrained by experimental RH values for ESCRT-0 reveal a dynamic ensemble of conformations well suited for diverse functions.
人类的Hrs和STAM蛋白组成了ESCRT-0复合物,该复合物将泛素化的细胞表面受体分选到溶酶体进行降解。在此,我们基于Hrs-STAM核心复合物的晶体结构、先前解析的结构域结构、流体动力学测量以及蒙特卡罗模拟,报告了完整ESCRT-0复合物的模型。在昆虫细胞中表达的ESCRT-0具有7.9纳米的流体动力学半径,是一种1:1异源二聚体。ESCRT-0核心复合物的2.3埃晶体结构揭示了两个结构域交换的GAT结构域和一个反平行双链卷曲螺旋,类似于酵母ESCRT-0。ESCRT-0代表了一类结合了结构化和非结构化元件的生物分子组装体,具有动态和开放的构象,以确保在靶标识别方面的多功能性。受ESCRT-0实验性流体动力学半径值约束的粗粒度蒙特卡罗模拟揭示了一组非常适合多种功能的动态构象。