Scavenger receptor class B Type I (SR-BI) assembles into detergent-sensitive dimers and tetramers.
Scavenger receptor class B Type I (SR-BI) assembles into detergent-sensitive dimers and tetramers.
复制标题
B 类清道夫受体 I 型 (SR-BI) 组装成对去污剂敏感的二聚体和四聚体。
DOI：
10.1016/j.bbalip.2006.03.003
复制
发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Connelly,MargeryA
中科院分区：
文献类型：
--
作者：
Sahoo,Daisy;Darlington,YolandaF;Pop,Diana;Williams,DavidL;Connelly,MargeryA
高密度脂蛋白 (HDL) 在胆固醇反向转运 (RCT) 途径中发挥着重要作用，因此可预防心血管疾病。 RCT 的最后一步是胆固醇酯 (CE) 从 HDL 核心选择性转移到细胞，这是由 I 类 B 类清道夫受体 (SR-BI) 介导的。 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，其中 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与其自身寡聚。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 FPLC 和蓝色天然 PAGE 表明 SR-BI 形成复合物，其大小表明形成了单体、二聚体和四聚体。有趣的是，即使不存在 SR-BI 的 C 端胞质结构域，同源寡聚也会发生。最后，我们报道了 SR-BI 介导的胆固醇转运的抑制剂 BLT-1 和 SR-BI 假定的亮氨酸拉链区域的突变对 SR-BI 功能具有深远的影响，但是，它们不影响受体自关联。这些观察结果表明，即使受体无功能，SR-BI 同源寡聚也会发生。
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.