Kadurin Ivan, Huber Stephan, Gründer Stefan
Institute of Physiology II, University of Würzburg, Röntgenring 9, Würzburg, Germany.
Biochem J. 2009 Mar 15;418(3):587-94. doi: 10.1042/BJ20081662.
Stomatin is an integral membrane protein which is widely expressed in many cell types. It is accepted that stomatin has a unique hairpin-loop topology: it is anchored to the membrane with an N-terminal hydrophobic domain and the N- and C-termini are cytoplasmically localized. Stomatin is a prototype for a family of related proteins, containing among others MEC-2 (mechanosensory protein 2) from Caenorhabditis elegans, SLP (stomatin-like protein)-3 and podocin, all of which interact with ion channels to regulate their activity. Members of the stomatin family partly localize in DRMs (detergent-resistant membrane domains) enriched in cholesterol and sphingolipids. It has been proposed that a highly conserved proline residue in the middle of the hydrophobic domain directly binds cholesterol and that cholesterol binding is necessary for the regulation of ion channels. In the present study we show that a small part of the stomatin pool exists as a single-pass transmembrane protein rather than a hairpin-loop protein. The highly conserved proline residue is crucial for adopting the hairpin-loop topology: substitution of this proline residue by serine transfers the whole stomatin pool to the single-pass transmembrane form, which no longer localizes to DRMs. These results suggest that formation of the hairpin loop is inefficient and that the conserved proline residue is indispensable for formation of the hairpin loop. The single-pass transmembrane form exists also for SLP-3 and it should be considered that it mediates part of the physiological functions of stomatin and related proteins.
胃动蛋白是一种整合膜蛋白，在多种细胞类型中广泛表达。人们认为胃动蛋白具有独特的发夹环拓扑结构：它通过N端疏水结构域锚定在膜上，N端和C端位于细胞质中。胃动蛋白是一类相关蛋白质家族的原型，其中包括来自秀丽隐杆线虫的MEC - 2（机械感觉蛋白2）、SLP（胃动蛋白样蛋白）- 3和足突蛋白，它们都与离子通道相互作用以调节其活性。胃动蛋白家族的成员部分定位于富含胆固醇和鞘脂的耐去污剂膜结构域（DRMs）中。有人提出，疏水结构域中部一个高度保守的脯氨酸残基直接结合胆固醇，并且胆固醇结合对于离子通道的调节是必要的。在本研究中，我们表明一部分胃动蛋白以单次跨膜蛋白形式存在，而不是发夹环蛋白形式。高度保守的脯氨酸残基对于形成发夹环拓扑结构至关重要：用丝氨酸取代该脯氨酸残基会使整个胃动蛋白池转变为单次跨膜形式，不再定位于DRMs。这些结果表明发夹环的形成效率低下，并且保守的脯氨酸残基对于发夹环的形成是不可或缺的。SLP - 3也存在单次跨膜形式，应该认为它介导了胃动蛋白及相关蛋白的部分生理功能。
