Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers.
Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers.
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DOI：
10.1083/jcb.201104062
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发表时间：
2011-12-12
期刊：
影响因子：
--
通讯作者：
Drin G
中科院分区：
文献类型：
--
作者：
de Saint-Jean M;Delfosse V;Douguet D;Chicanne G;Payrastre B;Bourguet W;Antonny B;Drin G
酵母Kes 1 p/Osh 4p蛋白作为脂质膜之间的固醇/PI（4）P交换剂起作用，这表明通过磷酸肌醇代谢产生固醇梯度的可能性。奥什/Orp蛋白在细胞器之间转运固醇并参与磷酸肌醇代谢。这两个方面之间的联系仍然难以捉摸。使用新的检测，我们解决的影响OSH 4P/KES 1 P提取，交付，或运输脱氢麦角甾醇（DHE）的能力膜组合物。令人惊讶的是，磷脂酰肌醇4-磷酸（PI（4）P）特异性抑制DHE提取，因为PI（4）P本身被Osh 4p有效提取。我们解决了Osh 4p-PI（4）P复合物的结构，并揭示了Osh 4p如何选择性地取代PI（4）P的甾醇。最后，我们表明，Osh 4p迅速交换DHE PI（4）P，从而可以运输这两个脂质膜之间沿着相反的路线。这些结果表明，在一个模型中，Osh 4p运输固醇从ER到晚隔室精确的PI（4）P，反过来，运输PI（4）P向后。结合PI（4）P代谢，该运输循环将产生固醇梯度。因为识别PI（4）P的残基在Osh 4p同源物中是保守的，所以其它奥什/Orp是潜在的甾醇/磷酸肌醇磷酸交换剂。
The yeast Kes1p/Osh4p protein functions as a sterol/PI(4)P exchanger between lipid membranes, which suggests the possibility of creating a sterol gradient via phosphoinositide metabolism. Osh/Orp proteins transport sterols between organelles and are involved in phosphoinositide metabolism. The link between these two aspects remains elusive. Using novel assays, we address the influence of membrane composition on the ability of Osh4p/Kes1p to extract, deliver, or transport dehydroergosterol (DHE). Surprisingly, phosphatidylinositol 4-phosphate (PI(4)P) specifically inhibited DHE extraction because PI(4)P was itself efficiently extracted by Osh4p. We solve the structure of the Osh4p–PI(4)P complex and reveal how Osh4p selectively substitutes PI(4)P for sterol. Last, we show that Osh4p quickly exchanges DHE for PI(4)P and, thereby, can transport these two lipids between membranes along opposite routes. These results suggest a model in which Osh4p transports sterol from the ER to late compartments pinpointed by PI(4)P and, in turn, transports PI(4)P backward. Coupled to PI(4)P metabolism, this transport cycle would create sterol gradients. Because the residues that recognize PI(4)P are conserved in Osh4p homologues, other Osh/Orp are potential sterol/phosphoinositol phosphate exchangers.
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影响因子：
7.8
作者：
Li, Xinmin;Rivas, Marcos P;Fang, Min;Marchena, Jennifer;Mehrotra, Bharat;Chaudhary, Anu;Feng, Li;Prestwich, Glenn D;Bankaitis, Vytas A
通讯作者：
Bankaitis, Vytas A
DOI：
10.1083/jcb.200901145
发表时间：
2009-05-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Klemm RW;Ejsing CS;Surma MA;Kaiser HJ;Gerl MJ;Sampaio JL;de Robillard Q;Ferguson C;Proszynski TJ;Shevchenko A;Simons K
通讯作者：
Simons K
DOI：
10.1016/j.bbalip.2009.03.002
发表时间：
2009-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Mesmin B;Maxfield FR
通讯作者：
Maxfield FR
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
16.8
作者：
Drin, Guillaume;Casella, Jean-Francois;Antonny, Bruno
通讯作者：
Antonny, Bruno