CPx-type ATPases: a class of P-type ATPases that pump heavy metals

Solioz, Marc; Vulpe, Christopher D.

doi:10.1016/s0968-0004(96)20016-7

Cited by 436 publications

(386 citation statements)

References 29 publications

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“…Ag uptake by lysosomal membrane vesicles is stimulated by ATP hydrolysis So far, all known copper transporters are P-type ATPases [11]. We investigated if the lysosomal heavy metal ion transporter also belongs to this group of P-type ATPases.…”

Section: Carrier Mediated Uptake Of Iihm Ag In Lysosomal Membranementioning

confidence: 99%

Characterization of a heavy metal ion transporter in the lysosomal membrane

et al. 1998

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Lysosomes are thought to play a role in various aspects of heavy metal metabolism. In the present study we demonstrate for the first time the presence of a heavy metal ion transport protein in the lysosomal membrane. Uptake of radioactive silver both in highly purified lysosomal membrane vesicles and in purified intact lysosomes showed the typical kinetics of a carrier-mediated process. This transport was stimulated by ATP hydrolysis, and showed specificity for Ag + , Cu P+ , and Cd P+ . All biochemical properties of this lysosomal metal ion transporter could classify it as a heavy metal transporting P-type ATPase. Long Evans Cinnamon (LEC) rats, an animal model for the copper transport disorder Wilson disease, showed normal lysosomal silver transport.z 1998 Federation of European Biochemical Societies.

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Section: Carrier Mediated Uptake Of Iihm Ag In Lysosomal Membranementioning

confidence: 99%

Characterization of a heavy metal ion transporter in the lysosomal membrane

et al. 1998

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“…This motif has been proposed to form the membrane-located ion binding site (Bissig et al 2001). Due to the CPx-feature, these ATPases are referred to as 'CPx-type' ATPases, but they have also been classified as P1B-type ATPases (Solioz and Vulpe 1996;Lutsenko and Kaplan 1995). CPx-type ATPases are thought to have evolved before the non-heavy metal ATPases to serve in host defense against toxic metals.…”

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confidence: 99%

Structural model of the CopA copper ATPase of Enterococcus hirae based on chemical cross-linking

et al. 2008

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The CopA copper ATPase of Enterococcus hirae belongs to the family of heavy metal pumping CPx-type ATPases and shares 43% sequence similarity with the human Menkes and Wilson copper ATPases. Due to a lack of suitable protein crystals, only partial three-dimensional structures have so far been obtained for this family of ion pumps. We present a structural model of CopA derived by combining topological information obtained by intramolecular cross-linking with molecular modeling. Purified CopA was crosslinked with different bivalent reagents, followed by tryptic digestion and identification of cross-linked peptides by mass spectrometry. The structural proximity of tryptic fragments provided information about the structural arrangement of the hydrophilic protein domains, which was integrated into a three-dimensional model of CopA. Comparative modeling of CopA was guided by the sequence similarity to the calcium ATPase of the sarcoplasmic reticulum, Serca1, for which detailed structures are available. In addition, known partial structures of CPx-ATPase homologous to CopA were used as modeling templates. A docking approach was used to predict the orientation of the heavy metal binding domain of CopA relative to the core structure, which was verified by distance constraints derived from cross-links. The overall structural model of CopA resembles the Serca1 structure, but reveals distinctive features of CPx-type ATPases. A prominent feature is the positioning of the heavy metal binding domain. It features an orientation of the Cu binding ligands which is appropriate for the interaction with Cu-loaded metallochaperones in solution. Moreover, a novel model of the architecture of the intramembranous Cu binding sites could be derived.

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“…The association and dissociation curves were fitted with the BIAevaluation software. This resulted in an association rate constant k a of 4.3·10 4 Fig. 4.)…”

Section: Resultsmentioning

confidence: 99%

“…Although some of these operons are missing the equivalent of the E. hirae copB or copZ genes, they do possess the genes encoding CopY-like repressors and CPx-type heavy-metal ATPases [4], which presumably are copper efflux pumps. Sequence comparison of the putative cop promoter/ repressor binding regions in these organisms revealed a common motif, consisting of an inverted repeat of the sequence TACAnnTGTA.…”

Section: Discussionmentioning

confidence: 99%