Aller Stephen G, Unger Vinzenz M
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, P.O. Box 208024, New Haven, CT 06520-8024, USA.
Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3627-32. doi: 10.1073/pnas.0509929103. Epub 2006 Feb 24.
Human CTR1 is a high-affinity copper transporter that also mediates the uptake of the anticancer drug cisplatin by largely unknown transport mechanisms. Here we report the 6-A projection structure obtained for human CTR1 by using electron crystallography of 2D protein crystals in a native phospholipid bilayer. The projection of CTR1 reveals a symmetrical trimer that is <40 A wide. Notably, the center threefold axis of each trimer forms a region of very low electron density likely to be involved in copper translocation. The formation of a putative pore for metal ions at the interface of three identical subunits deviates from the structural design of typical primary and secondary active transporters and reveals that copper uptake transporters have a novel architecture that is structurally more closely related to channel proteins.
人铜转运蛋白1（CTR1）是一种高亲和力的铜转运体，它也通过很大程度上未知的转运机制介导抗癌药物顺铂的摄取。在此，我们报告了通过在天然磷脂双层中对二维蛋白质晶体进行电子晶体学研究获得的人CTR1的6-A投影结构。CTR1的投影显示出一个宽度小于40埃的对称三聚体。值得注意的是，每个三聚体的中心三重轴形成了一个电子密度非常低的区域，可能参与铜的转运。在三个相同亚基的界面处形成一个假定的金属离子孔，这与典型的初级和次级主动转运体的结构设计不同，表明铜摄取转运体具有一种新颖的结构，在结构上与通道蛋白更密切相关。
