在膜组装后,Sec18(NSF)和 Sec17(SNAP)会促进膜融合。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-12-01 Epub Date: 2024-10-30 DOI:10.1091/mbc.E24-10-0439
Hongki Song, Karina Lopes, Amy Orr, William Wickner
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引用次数: 0

摘要

驱动膜融合的能量可能来自完整的 SNARE 拉链,也可能来自 Sec17 和 Sec18,或者两者兼而有之。Sec17 和 Sec18 最初形成一个结合膜的复合物。Sec17、Sec18以及Sec17 N域上一个环的极性是它们相互依存的膜结合所必需的。为了确定Sec18和Sec17环的极性在到达膜后是否仍然是融合所必需的,将疏水跨膜(TM)锚固定在Sec17的N端,形成TM-Sec17。没有完全 SNARE 拉链能量的融合需要 Sec18 以及 Sec17 或 TM-Sec17。即使不需要膜靶向,TM-Sec17极性环也能强烈刺激Sec17/18驱动的融合。因此,Sec18 和 Sec17 极环首先是膜靶向所必需的,一旦结合,就会驱动快速融合。这些变量中的每一个--Sec17的缺失或存在、其N-环的极性、Sec18的添加或省略、SNARE拉链能量的畅通或减弱--对跨SNARE复合物的数量几乎没有影响,而是调节了对接膜的融合能力。
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After their membrane assembly, Sec18 (NSF) and Sec17 (SNAP) promote membrane fusion.

The energy that drives membrane fusion can come from either complete SNARE zippering, from Sec17 and Sec18, or both. Sec17 and Sec18 initially form a complex which binds membranes. Sec17, Sec18, and the apolarity of a loop on the N-domain of Sec17 are required for their interdependent membrane association. To determine whether Sec18 and the Sec17 loop apolarity are still required for fusion after their membrane arrival, a hydrophobic transmembrane (TM) anchor was affixed to the N-terminus of Sec17, forming TM-Sec17. Fusion without energy from complete SNARE zippering requires Sec18 as well as either Sec17 or TM-Sec17. Even without the need for membrane targeting, the TM-Sec17 apolar loop strongly stimulates Sec17/18-driven fusion. Thus, Sec18 and the Sec17 apolar loop are first required for membrane targeting, and once bound, drive rapid fusion. Each of these variables-the absence or presence of Sec17, its N-loop apolarity, addition or omission of Sec18, and unimpeded or diminished energy from SNARE zippering-has almost no effect on the amount of trans-SNARE complex, but instead regulates the capacity of docked membranes to fuse.

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