Unknown

Dataset Information

0

Mechanism of Cu+-transporting ATPases: soluble Cu+ chaperones directly transfer Cu+ to transmembrane transport sites.


ABSTRACT: As in other P-type ATPases, metal binding to transmembrane metal-binding sites (TM-MBS) in Cu(+)-ATPases is required for enzyme phosphorylation and subsequent transport. However, Cu(+) does not access Cu(+)-ATPases in a free (hydrated) form but is bound to a chaperone protein. Cu(+) transfer from Cu(+) chaperones to regulatory cytoplasmic metal-binding domains (MBDs) present in these ATPases has been described, but there is no evidence of a proposed subsequent Cu(+) movement from the MBDs to the TM-MBS. Alternatively, we postulate the parsimonious Cu(+) transfer by the chaperone directly to TM-MBS. Testing both models, the delivery of Cu(+) by Archaeoglobus fulgidus Cu(+) chaperone CopZ to the corresponding Cu(+)-ATPase, CopA, was studied. As expected, CopZ interacted with and delivered the metal to CopA MBDs. Cu(+)-loaded MBDs, acting as metal donors, were unable to activate CopA or a truncated CopA lacking MBDs. Conversely, Cu(+)-loaded CopZ activated the CopA ATPase and CopA constructs in which MBDs were rendered unable to bind Cu(+). Furthermore, under nonturnover conditions, CopZ transferred Cu(+) to the TM-MBS of a CopA lacking MBDs. These data are consistent with a model where MBDs serve a regulatory function without participating in metal transport and the chaperone delivers Cu(+) directly to transmembrane transport sites of Cu(+)-ATPases.

SUBMITTER: Gonzalez-Guerrero M 

PROVIDER: S-EPMC2329688 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Mechanism of Cu+-transporting ATPases: soluble Cu+ chaperones directly transfer Cu+ to transmembrane transport sites.

González-Guerrero Manuel M   Argüello José M JM  

Proceedings of the National Academy of Sciences of the United States of America 20080415 16


As in other P-type ATPases, metal binding to transmembrane metal-binding sites (TM-MBS) in Cu(+)-ATPases is required for enzyme phosphorylation and subsequent transport. However, Cu(+) does not access Cu(+)-ATPases in a free (hydrated) form but is bound to a chaperone protein. Cu(+) transfer from Cu(+) chaperones to regulatory cytoplasmic metal-binding domains (MBDs) present in these ATPases has been described, but there is no evidence of a proposed subsequent Cu(+) movement from the MBDs to the  ...[more]

Similar Datasets

| S-EPMC2573086 | biostudies-literature
| S-EPMC3537068 | biostudies-literature
| S-EPMC4467857 | biostudies-literature
| S-EPMC2742845 | biostudies-literature
| S-EPMC10973460 | biostudies-literature
| S-EPMC3308323 | biostudies-literature
| S-EPMC4119550 | biostudies-literature
| S-EPMC3319165 | biostudies-literature
| S-EPMC5924815 | biostudies-literature
| S-EPMC3092005 | biostudies-literature