Getting In or Out: Early Segregation Between Importers and Exporters in the Evolution of ATP-Binding Cassette (ABC) Transporters

Abstract

ATP-binding cassette (ABC) systems, also called traffic ATPases, are found in eukaryotes and prokaryotes and almost all participate in the transport of a wide variety of molecules. ABC systems are characterized by a highly conserved ATPase module called here the ABC module, involved in coupling transport to ATP hydrolysis. We have used the sequence of one of the first representatives of bacterial ABC transporters, the MalK protein, to collect 250 closely related sequences from a nonredundant protein sequence database. The sequences collected by this objective method are all known or putative ABC transporters. After having eliminated short protein sequences and duplicates, the 197 remaining sequences were subjected to a phylogenetic analysis based on a mutational similarity matrix. An unrooted tree for these modules was found to display two major branches, one grouping all collected uptake systems and the other all collected export systems. This remarkable disposition strongly suggests that the divergence between these two functionally different types of ABC systems occurred once in the history of these systems and probably before the differentiation of prokaryotes and eukaryotes. We discuss the implications of this finding and we propose a model accounting for the generation and the diversification of ABC systems.

Identification and Characterization of anAzotobacter vinelandiiType I Secretion System Responsible for Export of the AlgE-Type Mannuronan C-5-Epimerases

“…Therefore, to ensure an open-minded genome survey, no ABC proteins were initially excluded from the analysis. To analyze the 85 sequences in more detail, we then aligned the most conserved subregions in their ABCs (in this text referred to as the A regions), essentially as described by Saurin et al (52). A set of A regions of experimentally verified type I ABC transporters from other bacteria was also included in the alignment to facilitate the identification of phylogenetic branches with potential type I sequences.…”

“…Only sequences passing this test were subjected to further analysis. The A regions from these sequences (a region comprising approximately 30 residues upstream of Walker A [Ge-valvGpsGsGKstll] to the end of Walker B [illlDEptsalD]) were extracted from each ABC protein as described by Saurin et al (52). The glycine in Walker A, indicated in bold above, was generally positioned as residue 43 in the extracted sequences, and the residues shown in capital letters are those that are most conserved.…”

Comparative Genomics and Adaptive Selection of the ATP-Binding-Cassette Gene Family in Caenorhabditis Species

“…In eukaryotes, ABC transporter genes are involved only in export (Saurin et al 1999). Here we conducted a comparative analysis of the ABC family between the three closely related nematode species C. elegans, C. briggsae, and C. remanei and inferred the phylogenetic relationship among the genes by ortholog clustering in a phylogenetic tree and intron/exon structure comparison of ABCE members.…”

“…In eukaryotes, the majority of ABC transporter proteins are involved in exporting compounds across cytoplasmic membranes or into intracellular compartments such as the endoplasmic reticulum or mitochondria. No eukaryotic ABC transporter has been found to be involved in import of compounds from outside the cell (Saurin et al 1999). A typical ABC transporter consists of at least one evolutionarily conserved ABC domain (also known as the nucleotide-binding domain, or the NBD), comprising $200 amino acid residues and a transmembrane domain (TMD) containing several predicted transmembrane a-helices.…”

Mechanism of ABC transporters: A molecular dynamics simulation of a well characterized nucleotide-binding subunit

“…These proteins share a common architectural organization comprising two hydrophilic nucleotidebinding domains (NBDs) located at the cytoplasmic surface of the membrane and two hydrophobic TM domains (TMDs) that form the translocation pathway. In prokaryotes, these domains are mostly expressed as separate protein subunits, whereas in eukaryotes they are usually fused into a single polypeptide (2). ABC transporter NBDs contain the Walker A and Walker B consensus sequences (3) characteristic of ATP-binding P-loop proteins (4), as well as a highly conserved ''LSGGQ'' signature sequence or C-motif (5).…”