Bro1 binds the Vps20 subunit of ESCRT-III and promotes ESCRT-III regulation by Doa4.
Bro1 binds the Vps20 subunit of ESCRT-III and promotes ESCRT-III regulation by Doa4.
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DOI：
10.1111/tra.12828
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Odorizzi G
中科院分区：
文献类型：
--
作者：
Buysse D;West M;Leih M;Odorizzi G
腔内囊泡（ILV）在内体的萌发需要ESCRT-III复合物进行膜断裂。该步骤在酵母中由Doa 4负调控，Doa 4是将作为货物分选到ILV中的跨膜蛋白去泛素化的泛素水解酶。Doa 4通过直接结合ESCRT-III的Snf 7亚基而非酶促地抑制ESCRT-III膜断裂活性。这种相互作用抑制ILV膜断裂反应所需的Snf 7聚合物的重塑/分解。因此，Doa 4被认为具有延迟ILV出芽的结构作用，同时它还具有酶促去泛素化ILV货物的功能。在这项研究中，我们表明，Doa 4结合到Snf 7在体内被另一个ESCRT-III亚基，Vps 20拮抗。在表达组成型结合Doa 4的突变Vps 20等位基因的酵母中，Doa 4被限制与Snf 7相互作用。Vps 20的这种抑制作用被另一种ESCRT-III相关蛋白Bro 1的过表达所抑制。我们发现，Bro 1直接结合到Vps 20，这表明Bro 1在缓解Vps 20对Doa 4的拮抗关系中具有核心作用。在酵母中，Doa 4泛素水解酶将作为货物分选的跨膜蛋白去泛素化到核内体处的腔内囊泡中。Doa 4还通过结合ESCRT-III复合物的Snf 7亚基而非催化地起作用，其调节ESCRT-III的膜断裂活性。Doa 4的催化和非催化功能通过其与ESCRT-III的Vps 20亚基的相互作用而被抑制。这种抑制作用被Bro 1蛋白所缓解，Bro 1蛋白直接与Vps 20结合。
The budding of intralumenal vesicles (ILVs) at endosomes requires membrane scission by the ESCRT-III complex. This step is negatively regulated in yeast by Doa4, the ubiquitin hydrolase that deubiquitinates transmembrane proteins sorted as cargoes into ILVs. Doa4 acts non-enzymatically to inhibit ESCRT-III membrane scission activity by directly binding the Snf7 subunit of ESCRT-III. This interaction inhibits the remodeling/disassembly of Snf7 polymers required for the ILV membrane scission reaction. Thus, Doa4 is thought to have a structural role that delays ILV budding while it also functions enzymatically to deubiquitinate ILV cargoes. In this study, we show that Doa4 binding to Snf7 in vivo is antagonized by another ESCRT-III subunit, Vps20. Doa4 is restricted from interacting with Snf7 in yeast expressing a mutant Vps20 allele that constitutively binds Doa4. This inhibitory effect of Vps20 is suppressed by overexpression of another ESCRT-III-associated protein, Bro1. We show that Bro1 binds directly to Vps20, suggesting that Bro1 has a central role in relieving the antagonistic relationship that Vps20 has toward Doa4. In yeast, the Doa4 ubiquitin hydrolase deubiquitinates transmembrane proteins sorted as cargoes into intralumenal vesicles at endosomes. Doa4 also functions non-catalytically by binding the Snf7 subunit of the ESCRT-III complex, which regulates the membrane scission activity of ESCRT-III. The calaytic and non-catalytic functions of Doa4 are inhibited through its interaction with the Vps20 subunit of ESCRT-III. This inhibition is relieved by the Bro1 protein, which binds directly to Vps20.
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影响因子：
64.5
作者：
Katzmann, DJ;Babst, M;Emr, SD
通讯作者：
Emr, SD
影响因子：
11.8
作者：
Pashkova, Natasha;Gakhar, Lokesh;Winistorfer, Stanley C.;Sunshine, Anna B.;Rich, Matthew;Dunham, Maitreya J.;Yu, Liping;Piper, Robert C.
通讯作者：
Piper, Robert C.
影响因子：
4
作者：
Odorizzi, G;Katzmann, DJ;Emr, SD
通讯作者：
Emr, SD
DOI：
10.1073/pnas.0801567105
发表时间：
2008-06-03
影响因子：
11.1
作者：
McCullough, John;Fisher, Robert D.;Hill, Christopher P.
通讯作者：
Hill, Christopher P.
DOI：
10.1083/jcb.200606113
发表时间：
2006-12-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nickerson DP;West M;Odorizzi G
通讯作者：
Odorizzi G