3D-DATA COLLECTION FROM 2D-CRYSTALS OF THE HUMAN COPPER TRANSPORTER HCTR1

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。CTR蛋白是介导除细菌以外的所有生物体细胞铜吸收的膜蛋白。敲除研究表明，CTR蛋白是生命所必需的，最近的遗传研究也确定CTR蛋白是铂基抗癌药物的主要入口途径。尽管它们很重要，但人们对CTR蛋白、它们的结构以及它们的设计如何促进铜和结构上不相关的更大的铂化合物的易位知之甚少。此外，铜被装载到转运蛋白中并传递到高度特异性的细胞内铜分子伴侣的集合的机制充其量是神秘的。我们的工作重点是确定的结构的人高亲和力铜转运蛋白hCTR 1，嵌入在脂质双层，通过电子晶体学，并使用我们的结构数据来阐明hCTR 1与其他蛋白质组分相互作用的机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. CTR-proteins are integral membrane proteins that mediate cellular copper uptake in all organisms except bacteria. Knock out studies have shown that CTR-proteins are essential for life, and recent genetic studies also identified CTR-proteins as the main entrance route for platinum based anti-cancer drugs. Despite their importance, very little is known about CTR-proteins, their structure and how their design facilitates translocation of copper and the structurally unrelated, much larger platinum compounds. Moreover, the mechanisms by which copper is loaded into the transporter and passed on to a collection of highly specific intracellular copper chaperons are mysterious at best. Our work is focused on determining the structure of the human high-affinity copper transporter hCTR1, embedded in a lipid bilayer, by electron crystallography, and to use our structural data to elucidate the mechanism by which hCTR1 interacts with other protein components.