期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：1
页码：95-100
DOI：10.1073/pnas.1117515109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Copper metallochaperones supply copper to cupro-proteins through copper-mediated protein-protein-interactions and it has been hypothesized that metallochaperones thereby inhibit copper from causing damage en route. Evidence is presented in support of this latter role for cyanobacterial metallochaperone, Atx1. In cyanobacteria Atx1 contributes towards the supply of copper to plastocyanin inside thylakoids but it is shown here that in copper-replete medium, copper can reach plastocyanin without Atx1. Unlike metallochaperone-independent copper-supply to superoxide dismutase in eukaryotes, glutathione is not essential for Atx1-independent supply to plastocyanin: Double mutants missing atx1 and gshB (encoding glutathione synthetase) accumulate the same number of atoms of copper per cell in the plastocyanin pool as wild type. Critically, {Delta}atx1{Delta}gshB are hypersensitive to elevated copper relative to wild type cells and also relative to {Delta}gshB single mutants with evidence that hypersensitivity arises due to the mislocation of copper to sites for other metals including iron and zinc. The zinc site on the amino-terminal domain (ZiaAN) of the P1-type zinc-transporting ATPase is especially similar to the copper site of the Atx1 target PacSN, and ZiaAN will bind Cu(I) more tightly than zinc. An NMR model of a substituted-ZiaAN-Cu(I)-Atx1 heterodimer has been generated making it possible to visualize a juxtaposition of residues surrounding the ZiaAN zinc site, including Asp18, which normally repulse Atx1. Equivalent repulsion between bacterial copper metallochaperones and the amino-terminal regions of P1-type ATPases for metals other than Cu(I) is conserved, again consistent with a role for copper metallochaperones to withhold copper from binding sites for other metals.
关键词：copper chaperone ; P1 type ATPase ; zinc sensors ; Zur ; synechocystis PCC 6803
