De Feo Christopher J, Aller Stephen G, Unger Vinzenz M
Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, P.O. Box 208024, New Haven, CT 06520-8024, USA.
Biometals. 2007 Jun;20(3-4):705-16. doi: 10.1007/s10534-006-9054-7. Epub 2007 Jan 9.
Over a decade ago, genetic studies identified a family of small integral membrane proteins, commonly referred to as copper transporters (CTRs) that are both required and sufficient for cellular copper uptake in a yeast genetic complementation assay. We recently used electron crystallography to determine a projection density map of the human high affinity transporter hCTR1 embedded into a lipid bilayer. At 6 A resolution, this first glimpse of the structure revealed that hCTR1 is trimeric and possesses the type of radial symmetry that traditionally has been associated with the structure of certain ion channels such as potassium or gap junction channels. Representative for this particular type of architecture, a region of low protein density at the center of the trimer is consistent with the existence of a copper permeable pore along the center three-fold axis of the trimer. In this contribution, we will briefly discuss how recent structure-function studies correlate with the projection density map, and provide a perspective with respect to the cellular uptake of other transition metals.
十多年前，遗传学研究鉴定出了一类小的整合膜蛋白家族，通常被称为铜转运蛋白（CTRs），在酵母遗传互补试验中，这些蛋白对于细胞摄取铜既是必需的也是充分的。我们最近利用电子晶体学确定了嵌入脂质双层中的人类高亲和力转运蛋白hCTR1的投影密度图。在6埃分辨率下，对该结构的首次观察表明，hCTR1是三聚体，具有传统上与某些离子通道（如钾通道或间隙连接通道）结构相关的径向对称类型。作为这种特殊结构类型的代表，三聚体中心蛋白质密度较低的区域与沿三聚体中心三重轴存在铜渗透孔一致。在本论文中，我们将简要讨论最近的结构-功能研究如何与投影密度图相关联，并就其他过渡金属的细胞摄取提供一个观点。
