Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor.
Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor.
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DOI：
10.1083/jcb.200707165
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发表时间：
2007-11-19
影响因子：
7.8
通讯作者：
Engelmann, Bernd
中科院分区：
文献类型：
--
作者：
Baumgaertner, Petra;Geiger, Margarethe;Zieseniss, Susanne;Malleier, Julia;Huntington, James A.;Hochrainer, Karin;Bielek, Edith;Stoeckelhuber, Mechthild;Lauber, Kirsten;Scherfeld, Dag;Schwille, Petra;Waeldele, Katja;Beyer, Klaus;Engelmann, Bernd
虽然他们的贡献仍然不清楚，脂质可能有助于非经典的蛋白质内化到细胞的途径，如细胞穿透蛋白所使用的。我们表明，蛋白C抑制剂（PCI），丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂），迅速穿越质膜，这在低温下持续存在，并使其核靶向在体外和体内。PCI的细胞膜转位必然需要磷脂酰乙醇胺（PE）。同时，PCI作为PE的脂质转移酶。内化的丝氨酸蛋白酶抑制剂促进细菌的吞噬作用，从而表明在宿主防御中的功能。PCI的膜插入取决于PE的圆锥形状，并且与膜内受限的水室的形成相关。获得和丧失功能的突变表明，PCI的跨膜通道需要一个分支的空腔之间的螺旋H和D，其中，根据对接研究，精确地容纳PE。我们的研究结果表明，其特定的形状使细胞表面PE驱动质膜易位的细胞穿透PCI。
Although their contribution remains unclear, lipids may facilitate noncanonical routes of protein internalization into cells such as those used by cell-penetrating proteins. We show that protein C inhibitor (PCI), a serine protease inhibitor (serpin), rapidly transverses the plasma membrane, which persists at low temperatures and enables its nuclear targeting in vitro and in vivo. Cell membrane translocation of PCI necessarily requires phosphatidylethanolamine (PE). In parallel, PCI acts as a lipid transferase for PE. The internalized serpin promotes phagocytosis of bacteria, thus suggesting a function in host defense. Membrane insertion of PCI depends on the conical shape of PE and is associated with the formation of restricted aqueous compartments within the membrane. Gain- and loss-of-function mutations indicate that the transmembrane passage of PCI requires a branched cavity between its helices H and D, which, according to docking studies, precisely accommodates PE. Our findings show that its specific shape enables cell surface PE to drive plasma membrane translocation of cell-penetrating PCI.
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影响因子：
4.8
作者：
BILLY, D;WILLEMS, GM;LINDHOUT, T
通讯作者：
LINDHOUT, T
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
7.8
作者：
de Kruijff, B
通讯作者：
de Kruijff, B
影响因子：
6.7
作者：
Geiger, Margarethe
通讯作者：
Geiger, Margarethe
影响因子：
4.8
作者：
Bogdanov, M;Umeda, M;Dowhan, W
通讯作者：
Dowhan, W