The structure and function of heavy metal transport P1B-ATPases

Abstract

P(1B)-type ATPases transport heavy metals (Cu+, Cu2+, Zn2+, Co2+, Cd2+, Pb2+) across membranes. Present in most organisms, they are key elements for metal homeostasis. P(1B)-type ATPases contain 6-8 transmembrane fragments carrying signature sequences in segments flanking the large ATP binding cytoplasmic loop. These sequences made possible the differentiation of at least four P(1B)-ATPase subgroups with distinct metal selectivity: P(1B-1): Cu+, P(1B-2): Zn2+, P(1B-3): Cu2+, P(1B-4): Co2+. Mutagenesis of the invariant transmembrane Cys in H6, Asn and Tyr in H7 and Met and Ser in H8 of the Archaeoglobus fulgidus Cu+-ATPase has revealed that their side chains likely coordinate the metals during transport and constitute a central unique component of these enzymes. The structure of various cytoplasmic domains has been solved. The overall structure of those involved in enzyme phosphorylation (P-domain), nucleotide binding (N-domain) and energy transduction (A-domain), appears similar to those described for the SERCA Ca2+-ATPase. However, they show different features likely associated with singular functions of these proteins. Many P(1B)-type ATPases, but not all of them, also contain a diverse arrangement of cytoplasmic metal binding domains (MBDs). In spite of their structural differences, all N- and C-terminal MBDs appear to control the enzyme turnover rate without affecting metal binding to transmembrane transport sites. In addition, eukaryotic Cu+-ATPases have multiple N-MBD regions that participate in the metal dependent targeting and localization of these proteins. The current knowledge of structure-function relationships among the different P(1B)-ATPases allows for a description of selectivity, regulation and transport mechanisms. Moreover, it provides a framework to understand mutations in human Cu+-ATPases (ATP7A and ATP7B) that lead to Menkes and Wilson diseases.

A Member of the Heavy Metal P-Type ATPase OsHMA5 Is Involved in Xylem Loading of Copper in Rice

“…These results provided direct evidence of Cu transport mediated by OsHMA5 protein in yeast. Guerinot, 2006; Argüello et al, 2007;Burkhead et al, 2009). The functional characterization of OsHMA5 in this study showed that it transports Cu and is involved in the xylem loading of Cu at the both vegetative and reproductive growth stages (Figs.…”

“…A number of different transporters, such as Cation Diffusion Facilitator, Natural resistance-associated macrophage protein, ATPBinding Cassette, Zinc-and Iron-regulated-like Protein, and P-type ATPase, have been reported to be involved in the uptake, translocation, distribution, and homeostasis of nutrients (Hall and Williams, 2003;Krämer et al, 2007;Palmer and Guerinot, 2009). Among them, heavy metal-transporting P-type ATPase (HMA), the P 1B subfamily of the P-type ATPase superfamily, has been implicated in heavy metal transport (Williams and Mills, 2005;Grotz and Guerinot, 2006;Argüello et al, 2007;Burkhead et al, 2009). There are eight and nine members of P 1B -ATPase in Arabidopsis thaliana and rice (Oryza sativa), respectively (Williams and Mills, 2005).…”

Dissecting the Salmonella response to copper

“…Among these systems, transporters of the P-type ATPases family (Arguello et al, 2007;Kuhlbrandt, 2004) are usually involved. We have demonstrated here that expression of the Salmonella P-type ATPase CopA is induced by copper ions in a CueR-dependent manner (Figs 1 and 2) and that deletion of the copA gene affects copper tolerance under both aerobic and anaerobic conditions (Table 3).…”

A P-type ATPase importer that discriminates between essential and toxic transition metals

“…The majority of characterized pumps fall into one of the following categories: efflux pumps involved in detoxification of monovalent metals (copper † and silver) or efflux pumps involved in detoxification of divalent metals (zinc, cadmium, and mercury). These two groups differ in the presence of unique amino acid sequences in their transmembrane domains, presumably contributing to substrate specificity (7,8). This notion is further supported by functional analysis of various P-type pumps harboring these amino acid motifs.…”