Diversity of the metal-transporting P1B-type ATPases

Abstract

The P1B-ATPases are integral membrane proteins that couple ATP hydrolysis to metal cation transport. Widely distributed across all domains of life, these enzymes have been previously shown to transport copper, zinc, cobalt, and other thiophilic heavy metals. Recent data suggest that these enzymes may also be involved in nickel and/or iron transport. Here we have exploited large amounts of genomic data to examine and classify the various P1B-ATPase subfamilies. Specifically, we have combined new methods of data partitioning and network visualization known as Transitivity Clustering and Protein Similarity Networks with existing biochemical data to examine properties such as length, speciation, and metal-binding motifs of the P1B-ATPase subfamily sequences. These data reveal interesting relationships among the enzyme sequences of previously established subfamilies, indicate the presence of two new subfamilies, and suggest the existence of new regulatory elements in certain subfamilies. Taken together, these findings underscore the importance of P1B-ATPases in homeostasis of nearly every biologically relevant transition metal and provide an updated framework for future studies.

The PerR-Regulated P 1B-4 -Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes

“…However, there are multiple subclasses of class P 1B -type ATPases in bacteria, each with various metal specificities. Metal ion specificity has previously been shown to depend on specific amino acid sequences within transmembrane (TM) regions of the protein (26). In order to classify PmtA within P-type ATPase class designations, an amino acid alignment of GAS PmtA with other annotated P 1B-4 -type ATPases from different bacteria (NCBI nonredundant GenBank database) was performed using MUSCLE (27).…”

“…Sequences that share homology with S. pyogenes PmtA (see Table S1 in the supplemental material) were identified on the basis of a BLASTP search of the nonredundant GenBank database (NCBI) and included functionally characterized P 1B-4 ATPase amino acid sequences from B. subtilis PfeT (GenBank accession number CUB17201.1), L. monocytogenes FrvA (accession number NP_464168), and GAS PmtA (accession number AAZ51785.1). Determination of the P-type ATPase subclass was performed by using previously described methods (26). Protein sequences were aligned by using MUSCLE v3.8.31 (27) and trimmed to the common transmembrane domains 1 and 6 relative to the well-characterized PfeT protein from Bacillus subtilis (18).…”

Cadmium and Secondary Structure-dependent Function of a Degron in the Pca1p Cadmium Exporter

“…Endocytosis and degradation of a human zinc importer in a histidine-rich, cluster-dependent manner protects against zinc cytotoxicity (63). Several other P 1B -type ATPase family members in mammals and plants to which Pca1p belongs possess undercharacterized metal-binding residues at the N or C terminus (64). The predicted metal binding sites might play roles for regulation of activities, expression, and/or subcellular trafficking of those transporters.…”

Roles of Agrobacterium tumefaciens C58 ZntA and ZntB and the transcriptional regulator ZntR in controlling Cd2+/Zn2+/Co2+ resistance and the peroxide stress response

“…It has been reported that ZntA (a P 1B -type ATPase) and ZntB (a transporter belonging to the 2-TM-GxN family) are zinc exporters (Knoop et al, 2005;Smith et al, 2014 (Beard et al, 1997;Rensing et al, 1997Rensing et al, , 1998Binet & Poole, 2000), Staphylococcus aureus ZntA (ZntA Sa ) exports Co 2+ (Xiong & Jayaswal, 1998), and S. enterica ZntB (ZntB St ) mediates the efflux of Cd 2+ (Worlock & Smith, 2002). The genomic context of A. tumefaciens zntR, zntA and zntB is shown in Fig.…”