Sahoo Daisy, Darlington Yolanda F, Pop Diana, Williams David L, Connelly Margery A
Department of Pharmacological Sciences, University Medical Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA.
Biochim Biophys Acta. 2007 Jul;1771(7):807-17. doi: 10.1016/j.bbalip.2006.03.003. Epub 2006 Mar 31.
High density lipoproteins (HDL) are protective against cardiovascular disease due to their important role in the reverse cholesterol transport (RCT) pathway. The selective transfer of cholesteryl ester (CE) from the HDL core to cells, the last step in RCT, is mediated by scavenger receptor class B type I (SR-BI). SR-BI is a heavily glycosylated cell surface receptor that is highly expressed in the liver, ovaries, testes and adrenal glands, where selective uptake of HDL-CE is most prevalent. Previous studies have shown that SR-BI oligomerizes with itself in steroidogenic tissues as well as in diverse cell lines. In the present study, we provide further evidence for the homo-oligomerization of SR-BI. We show by FPLC and blue native PAGE that SR-BI forms complexes whose sizes suggest the formation of monomers, dimers, and tetramers. Interestingly, homo-oligomerization occurs even with the absence of SR-BI's C-terminal cytoplasmic domain. Finally, we report that an inhibitor of SR-BI-mediated cholesterol transport, BLT-1, and mutations in the putative leucine zipper region of SR-BI have profound effects on SR-BI function, however, they do not affect receptor self-association. These observations indicate that SR-BI homo-oligomerization occurs even when the receptor is non-functional.
高密度脂蛋白（HDL）因其在胆固醇逆向转运（RCT）途径中的重要作用而对心血管疾病具有保护作用。胆固醇酯（CE）从HDL核心向细胞的选择性转移是RCT的最后一步，由I型清道夫受体B类（SR-BI）介导。SR-BI是一种高度糖基化的细胞表面受体，在肝脏、卵巢、睾丸和肾上腺中高度表达，这些部位对HDL-CE的选择性摄取最为普遍。先前的研究表明，SR-BI在类固醇生成组织以及多种细胞系中会自身寡聚化。在本研究中，我们为SR-BI的同源寡聚化提供了进一步的证据。我们通过快速蛋白质液相色谱（FPLC）和蓝色天然聚丙烯酰胺凝胶电泳（blue native PAGE）表明，SR-BI形成的复合物大小表明形成了单体、二聚体和四聚体。有趣的是，即使没有SR-BI的C末端胞质结构域，同源寡聚化也会发生。最后，我们报告称，SR-BI介导的胆固醇转运抑制剂BLT-1以及SR-BI假定的亮氨酸拉链区域的突变对SR-BI功能有深远影响，然而，它们并不影响受体的自我缔合。这些观察结果表明，即使受体无功能，SR-BI的同源寡聚化也会发生。
