Vps27-Hse1 and ESCRT-I complexes cooperate to increase efficiency of sorting ubiquitinated proteins at the endosome.
Vps27-Hse1 and ESCRT-I complexes cooperate to increase efficiency of sorting ubiquitinated proteins at the endosome.
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VPS27-HSE1和ESCRT-I复合物配合，以提高在内体处分类泛素化蛋白的效率。
DOI：
10.1083/jcb.200305007
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发表时间：
2003-10-27
影响因子：
7.8
通讯作者：
Piper, RC
中科院分区：
文献类型：
--
作者：
Bilodeau, PS;Winistorfer, SC;Kearney, WR;Robertson, AD;Piper, RC
泛素（Ub）附着于细胞表面蛋白，通过将其掺入多泡体（MVB）的管腔膜中而引起其溶酶体降解。两种酵母内体蛋白复合物已被提出作为Ub分选“受体”，Vps 27-Hse 1复合物和ESCRT-I复合物。我们使用NMR光谱和诱变研究来绘制Vps 27和Vps 23的Ub结合表面。仅消除Vps 27结合或Vps 23结合的Ub突变阻断了Ub作为MVB分选信号的能力，支持Vps 27-Hse 1和ESCRT-I复合物与泛素化货物相互作用的观点。Vps 27也通过存在于Vps 27 COOH末端内的两个PSDP基序直接结合Vps 23。Vps 27-Vps 23结合的丧失导致分选进入内体腔的效率较低。然而，液泡蛋白酶的分选或MVB的整体生物发生没有受到严重影响。相反，破坏Vps 27和Hse 1之间的相互作用引起严重的缺陷，羧肽酶Y分选和MVB形成。这些结果表明，这两个泛素-分选复合物耦合的有效识别泛素化货物。
Ubiquitin (Ub) attachment to cell surface proteins causes their lysosomal degradation by incorporating them into lumenal membranes of multivesicular bodies (MVBs). Two yeast endosomal protein complexes have been proposed as Ub-sorting “receptors,” the Vps27-Hse1 complex and the ESCRT-I complex. We used NMR spectroscopy and mutagenesis studies to map the Ub-binding surface for Vps27 and Vps23. Mutations in Ub that ablate only Vps27 binding or Vps23 binding blocked the ability of Ub to serve as an MVB sorting signal, supporting the idea that both the Vps27-Hse1 and ESCRT-I complexes interact with ubiquitinated cargo. Vps27 also bound Vps23 directly via two PSDP motifs present within the Vps27 COOH terminus. Loss of Vps27-Vps23 association led to less efficient sorting into the endosomal lumen. However, sorting of vacuolar proteases or the overall biogenesis of the MVB were not grossly affected. In contrast, disrupting interaction between Vps27 and Hse1 caused severe defects in carboxy peptidase Y sorting and MVB formation. These results indicate that both Ub-sorting complexes are coupled for efficient recognition of ubiquitinated cargo.
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影响因子：
64.5
作者：
Katzmann, DJ;Babst, M;Emr, SD
通讯作者：
Emr, SD
DOI：
10.1038/86208
发表时间：
2001-04-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Sivaraman, T;Arrington, CB;Robertson, AD
通讯作者：
Robertson, AD
影响因子：
4.8
作者：
Bache, KG;Raiborg, C;Stenmark, H
通讯作者：
Stenmark, H
影响因子：
7.7
作者：
Sakata, E;Yamaguchi, Y;Kato, K
通讯作者：
Kato, K
影响因子：
64.5
作者：
Garrus, JE;von Schwedler, UK;Sundquist, WI
通讯作者：
Sundquist, WI