Structure of the ESCRT-II endosomal trafficking complex
Structure of the ESCRT-II endosomal trafficking complex
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DOI：
10.1038/nature02914
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发表时间：
2004-09-09
期刊：
影响因子：
64.8
通讯作者：
Hurley, JH
中科院分区：
文献类型：
--
作者：
Hierro, A;Sun, J;Hurley, JH
多囊泡体(MVB)途径将跨膜蛋白和脂类输送到内体的管腔。多囊泡体分选途径在生长因子受体下调(1)、发育信号(2-4)、免疫反应的调节(5)和某些包膜病毒的萌发(如人类免疫缺陷病毒(6))中起着至关重要的作用。泛素化是分选进入MVB途径的信号(7，8)，这也需要三个蛋白质复合体的功能，称为ESCRT-I，-II和-III(运输所需的内体分选复合体)(7，9，10)。在这里，我们报道了酵母ESCRT-II复合体的核心的晶体结构，它包含一个VPS蛋白Vps22分子，Vps36的羧基末端结构域和两个Vps25分子，具有大写字母Y的形状。Vps22的氨基末端卷曲的卷曲和导致Vps36的泛素结合NZF结构域的柔性接头都从‘Y’的一个分支的末端突出。Vps22和Vps36与位于‘Y’中心的两个Vps25分子形成几乎相同的相互作用。该结构表明泛素化的货物如何通过泛素化的货物从一个复合体到下一个复合体的顺序转移在MVB途径的ESCRT组件之间传递。
The multivesicular-body (MVB) pathway delivers transmembrane proteins and lipids to the lumen of the endosome. The multivesicular-body sorting pathway has crucial roles in growth-factor-receptor downregulation(1), developmental signalling(2-4), regulation of the immune response(5) and the budding of certain enveloped viruses such as human immunodeficiency virus(6). Ubiquitination is a signal for sorting into the MVB pathway(7,8), which also requires the functions of three protein complexes, termed ESCRT-I, -II and -III (endosomal sorting complex required for transport)(7,9,10). Here we report the crystal structure of the core of the yeast ESCRT-II complex, which contains one molecule of the Vps protein Vps22, the carboxy-terminal domain of Vps36 and two molecules of Vps25, and has the shape of a capital letter 'Y'. The amino-terminal coiled coil of Vps22 and the flexible linker leading to the ubiquitin-binding NZF domain of Vps36 both protrude from the tip of one branch of the 'Y'. Vps22 and Vps36 form nearly equivalent interactions with the two Vps25 molecules at the centre of the 'Y'. The structure suggests how ubiquitinated cargo could be passed between ESCRT components of the MVB pathway through the sequential transfer of ubiquitinated cargo from one complex to the next.