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：2018
卷号：115
期号：9
页码：2108-2113
DOI：10.1073/pnas.1721783115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The copper-transporting P1B-ATPases, which play a key role in cellular copper homeostasis, have been divided traditionally into two subfamilies, the P1B-1-ATPases or CopAs and the P1B-3-ATPases or CopBs. CopAs selectively export Cu+ whereas previous studies and bioinformatic analyses have suggested that CopBs are specific for Cu2+ export. Biochemical and spectroscopic characterization of Sphaerobacter thermophilus CopB ( St CopB) show that, while it does bind Cu2+, the binding site is not the prototypical P1B-ATPase transmembrane site and does not involve sulfur coordination as proposed previously. Most important, St CopB exhibits metal-stimulated ATPase activity in response to Cu+, but not Cu2+, indicating that it is actually a Cu+ transporter. X-ray absorption spectroscopic studies indicate that Cu+ is coordinated by four sulfur ligands, likely derived from conserved cysteine and methionine residues. The histidine-rich N-terminal region of St CopB is required for maximal activity, but is inhibitory in the presence of divalent metal ions. Finally, reconsideration of the P1B-ATPase classification scheme suggests that the P1B-1- and P1B-3-ATPase subfamilies both comprise Cu+ transporters. These results are completely consistent with the known presence of only Cu+ within the reducing environment of the cytoplasm, which should eliminate the need for a Cu2+ P1B-ATPase.
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