The luminal N-terminus of yeast Nvj1 is an inner nuclear membrane anchor.
The luminal N-terminus of yeast Nvj1 is an inner nuclear membrane anchor.
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DOI：
10.1111/j.1600-0854.2008.00789.x
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发表时间：
2008-09
期刊：
影响因子：
--
通讯作者：
Goldfarb DS
中科院分区：
文献类型：
--
作者：
Millen JI;Pierson J;Kvam E;Olsen LJ;Goldfarb DS
脑鼠的内质网主要分为核周区室和皮质区室。酵母Nvj1只定位于核周内质网上的小块，在那里它与液泡膜上的Vac8相互作用，形成核-液泡（NV）连接。Nvj1的三个区域介导NV连接的生物发生。一个跨膜结构域将蛋白质靶向内质网。c端结合液泡膜上的Vac8，诱导两种蛋白聚集成NV连接。管腔n端是严格的核周定位所必需的。三维冷冻电子断层扫描显示，Nvj1将两个核膜之间的分离夹紧到体核膜宽度的一半。n端包含一个疏水序列，由类似于线粒体外膜信号锚点的基本残基包围。疏水序列可以被打乱或反转而不影响功能。降低核心序列疏水性或影响基本残基分布的突变会导致皮质内质网的错误定位。我们得出结论，Nvj1的n端是一个桥接核周管腔并插入内核膜的保留序列。
The endoplasmic reticulum (ER) in S. cerevisae is largely divided between perinuclear and cortical compartments. Yeast Nvj1 localizes exclusively to small patches on the perinuclear ER, where it interacts with Vac8 in the vacuole membrane to form nucleus-vacuole (NV) junctions. Three regions of Nvj1 mediate the biogenesis of NV junctions. A membrane-spanning domain targets the protein to the ER. The C-terminus binds Vac8 in the vacuole membrane, which induces the clustering of both proteins into NV junctions. The luminal N-terminus is required for strict perinuclear localization. 3D cryo-electron tomography reveals that Nvj1 clamps the separation between the two nuclear membranes to half the width of bulk nuclear envelope. The N-terminus contains a hydrophobic sequence bracketed by basic residues that resembles outer mitochondrial membrane signal-anchors. The hydrophobic sequence can be scrambled or reversed without affecting function. Mutations that reduce the hydrophobicity of the core sequence, or affect the distribution of basic residues, cause mislocalization to the cortical ER. We conclude that the N-terminus of Nvj1 is a retention sequence that bridges the perinuclear lumen and inserts into the inner nuclear membrane.
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