The binding of Varp to VAMP7 traps VAMP7 in a closed, fusogenically inactive conformation.

The binding of Varp to VAMP7 traps VAMP7 in a closed, fusogenically inactive conformation.
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DOI:
10.1038/nsmb.2414
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发表时间:
2012-12
影响因子:
16.8
通讯作者:
Owen, David J.
Owen, David J.
中科院分区:
生物学1区
文献类型:
--
作者:
Schaefer, Ingmar B.;Hesketh, Geoffrey G.;Bright, Nicholas A.;Gray, Sally R.;Pryor, Paul R.;Evans, Philip R.;Luzio, J. Paul;Owen, David J.

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SNARE为膜融合事件提供能量和特异性。融合反式SNARE复合物由嵌入一个膜中的Q-SNARE和嵌入另一个膜中的R-SNARE组装而成。膜融合事件的调节对于细胞内运输是至关重要的。我们确定内体蛋白Varp作为R-陷阱结合调节陷阱复合物的形成。Varp与VAMP 7共定位并结合,VAMP 7是一种参与内吞和分泌途径的R-SNARE。我们目前的结构的第二锚蛋白重复结构域的哺乳动物Varp在复杂的细胞溶质部分的VAMP 7。VAMP 7 SNARE基序被捕获在Varp和VAMP 7长蛋白结构域之间,因此Varp在动力学上抑制VAMP 7形成SNARE复合物的能力。当Varp也可以结合与VAMP 7相同的膜上存在的其他蛋白质如Rab 32:GTP时,这种抑制作用将增加。
SNAREs provide energy and specificity to membrane fusion events. Fusogenic trans-SNARE complexes are assembled from Q-SNAREs embedded in one membrane and an R–SNARE embedded in the other. Regulation of membrane fusion events is crucial for intracellular trafficking. We identify the endosomal protein Varp as an R-SNARE-binding regulator of SNARE complex formation. Varp co-localises with and binds to VAMP7, an R-SNARE involved in both endocytic and secretory pathways. We present the structure of the second ankyrin repeat domain of mammalian Varp in complex with the cytosolic portion of VAMP7. The VAMP7 SNARE motif is trapped between Varp and the VAMP7 longin domain and hence Varp kinetically inhibits VAMP7’s ability to form SNARE complexes. This inhibition will be increased when Varp can also bind to other proteins present on the same membrane as the VAMP7 such as Rab32:GTP.
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