期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 129, 期 50, 页码 15440-+出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja077146j
关键词
-
资金
- NIGMS NIH HHS [R01 GM065790, R01 GM065790-07, GM 65790] Funding Source: Medline
PrP binds copper in the highly conserved, unstructured N-terminal half of the protein. The octarepeat region consists of four tandem repeats of PHGGGWGQ and binds 4 equiv of copper at full occupancy. Adjacent to the octarepeats are two additional histidines that may also bind copper. We recently showed that, when the octarepeat region is titrated with Cu2+, the copper binding mode depends on the number of equivalents of copper bound. In addition to copper, other metals have been associated with PrP; however, zinc is the only metal other than copper that induces PrP endocytosis, inhibits fibril formation, and promotes intermolecular interactions. In this work, we show that even large excesses of zinc (> 1 mM) are unable to displace copper from either the octarepeat region or the full-length protein. However, EPR reveals that physiologically relevant levels of zinc significantly alter the distribution of copper among the available binding modes. Diethyl pyrocarbonate (DEPC) modification and mass spectrometry is used to identify the octarepeat region as the zinc binding site and to confirm that the affinity of PrP for zinc is similar to 200 mu M. PrP can simultaneously bind both copper and zinc by shifting to binding modes that minimize the ratio of histidines to copper.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据