Structural basis for assembly of TRAPPII complex and specific activation of GTPase Ypt31/32.

Structural basis for assembly of TRAPPII complex and specific activation of GTPase Ypt31/32.
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TRAPPII 复合物组装和 GTPase Ypt31/32 特异性激活的结构基础。

DOI:
10.1126/sciadv.abi5603
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发表时间:
2022-01-28
期刊:
影响因子:
13.6
通讯作者:
Sui SF
Sui SF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mi C;Zhang L;Huang G;Shao G;Yang F;You X;Dong MQ;Sun S;Sui SF

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转运蛋白颗粒(TRAPP)复合物属于多蛋白系聚复合物,存在核心TRAPP/TRAPPI、TRAPPII和TRAPPIII三种形式。TRAPPII激活GTPase Ypt31/Ypt32作为反式高尔基网络中的鸟嘌呤核苷酸交换因子,决定酵母中高尔基池向后高尔基载体的成熟。在这里,我们展示了apo和ypt32结合状态下酵母TRAPPII的低温电镜结构。所有结构均为由两个三角形单体组装而成的二聚体结构,而载子态的单体具有开放和封闭的构象,而ypt32结合形式的单体仅具有封闭的构象。Ypt32位于单体内部,通过其核苷酸结合域与核心TRAPP/TRAPPI和Trs120结合,并通过其高变结构域与Trs31结合。结合功能分析,这些结构揭示了TRAPPII的组装和TRAPPII特异性激活Ypt31/Ypt32的机制。不同状态下TRAPPII的结构揭示了TRAPPII特异性激活Ypt32的机制。
Transport protein particle (TRAPP) complexes belong to the multiprotein tethering complex and exist in three forms—core TRAPP/TRAPPI, TRAPPII, and TRAPPIII. TRAPPII activates GTPase Ypt31/Ypt32 as the guanine nucleotide exchange factor in the trans-Golgi network to determine the maturation of Golgi cisternae into post-Golgi carriers in yeast. Here, we present cryo-EM structures of yeast TRAPPII in apo and Ypt32-bound states. All the structures show a dimeric architecture assembled by two triangle-shaped monomers, while the monomer in the apo state exhibits both open and closed conformations, and the monomer in the Ypt32-bound form only captures the closed conformation. Located in the interior of the monomer, Ypt32 binds with both core TRAPP/TRAPPI and Trs120 via its nucleotide-binding domain and binds with Trs31 via its hypervariable domain. Combined with functional analysis, the structures provide insights into the assembly of TRAPPII and the mechanism of the specific activation of Ypt31/Ypt32 by TRAPPII. Structures of TRAPPII in different states reveal the mechanism of the specific activation of Ypt32 by TRAPPII.
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