Faculty of Life Sciences, Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
J Struct Biol. 2010 Jun;170(3):540-7. doi: 10.1016/j.jsb.2010.01.011. Epub 2010 Jan 28.
Multidrug resistance protein 1 (ABCC1) is a member of the 'C' class of ATP-binding cassette transporters, which can give rise to resistance to chemotherapy via drug export from cells. It also acts as a leukotriene C4 transporter, and hence has a role in adaptive immune response. Most C-class members have an additional NH(2)-terminal transmembrane domain versus other ATP-binding cassette transporters, but little is known about the structure and role of this domain. Using electron cryomicroscopy of 2D crystals, data at 1/6per A(-1) resolution was generated for the full-length ABCC1 protein in the absence of ATP. Analysis using homologous structures from bacteria and mammals allowed the core transmembrane domains to be localised in the map. These display an inward-facing conformation and there is a noteworthy separation of the cytoplasmic nucleotide-binding domains. Examination of non-core features in the map suggests that the additional NH(2)-terminal domain has extensive contacts on one side of both core domains, and mirrors their inward-facing configuration in the absence of nucleotide.
多药耐药蛋白 1（ABCC1）是“C”类 ATP 结合盒转运蛋白的成员，可通过将药物从细胞内输出而导致化疗耐药。它还作为白三烯 C4 转运蛋白发挥作用，因此在适应性免疫反应中具有作用。大多数 C 类成员相对于其他 ATP 结合盒转运蛋白具有额外的 NH2-末端跨膜结构域，但对此结构域的结构和作用知之甚少。使用 2D 晶体的电子 cryomicroscopy，在没有 ATP 的情况下生成了全长 ABCC1 蛋白的 1/6per A（-1）分辨率的数据。使用来自细菌和哺乳动物的同源结构的分析允许将核心跨膜结构域定位在图谱中。这些显示出内向构象，并且细胞质核苷酸结合结构域之间有明显的分离。在图谱中检查非核心特征表明，额外的 NH2-末端结构域在两个核心结构域的一侧有广泛的接触，并在没有核苷酸的情况下镜像其内向构象。
