Dataset Information

Selecting for Altered Substrate Specificity Reveals the Evolutionary Flexibility of ATP-Binding Cassette Transporters.

ABSTRACT: ATP-binding cassette (ABC) transporters are the largest family of ATP-hydrolyzing transporters, which import or export substrates across membranes, and have members in every sequenced genome. Structural studies and biochemistry highlight the contrast between the global structural similarity of homologous transporters and the enormous diversity of their substrates. How do ABC transporters evolve to carry such diverse molecules and what variations in their amino acid sequence alter their substrate selectivity? We mutagenized the transmembrane domains of a conserved fungal ABC transporter that exports a mating pheromone and selected for mutants that export a non-cognate pheromone. Mutations that alter export selectivity cover a region that is larger than expected for a localized substrate-binding site. Individual selected clones have multiple mutations, which have broadly additive contributions to specific transport activity. Our results suggest that multiple positions influence substrate selectivity, leading to alternative evolutionary paths toward selectivity for particular substrates and explaining the number and diversity of ABC transporters.

SUBMITTER: Srikant S

PROVIDER: S-EPMC7243462 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Selecting for Altered Substrate Specificity Reveals the Evolutionary Flexibility of ATP-Binding Cassette Transporters.

Srikant Sriram S Gaudet Rachelle R Murray Andrew W AW

Current biology : CB 20200326 9

ATP-binding cassette (ABC) transporters are the largest family of ATP-hydrolyzing transporters, which import or export substrates across membranes, and have members in every sequenced genome. Structural studies and biochemistry highlight the contrast between the global structural similarity of homologous transporters and the enormous diversity of their substrates. How do ABC transporters evolve to carry such diverse molecules and what variations in their amino acid sequence alter their substrate ...[more]

PMID: 32220325

Similar Datasets

Project description:BackgroundThe ATP-Binding Cassette (ABC) functional superfamily includes integral transmembrane exporters that have evolved three times independently, forming three families termed ABC1, ABC2 and ABC3, upon which monophyletic ATPases have been superimposed for energy-coupling purposes [e.g., J Membr Biol 231(1):1-10, 2009]. The goal of the work reported in this communication was to understand how the integral membrane constituents of ABC uptake transporters with different numbers of predicted or established transmembrane segments (TMSs) evolved. In a few cases, high resolution 3-dimensional structures were available, and in these cases, their structures plus primary sequence analyses allowed us to predict evolutionary pathways of origin.ResultsAll of the 35 currently recognized families of ABC uptake proteins except for one (family 21) were shown to be homologous using quantitative statistical methods. These methods involved using established programs that compare native protein sequences with each other, after having compared each sequence with thousands of its own shuffled sequences, to gain evidence for homology. Topological analyses suggested that these porters contain numbers of TMSs ranging from four or five to twenty. Intragenic duplication events occurred multiple times during the evolution of these porters. They originated from a simple primordial protein containing 3 TMSs which duplicated to 6 TMSs, and then produced porters of the various topologies via insertions, deletions and further duplications. Except for family 21 which proved to be related to ABC1 exporters, they are all related to members of the previously identified ABC2 exporter family. Duplications that occurred in addition to the primordial 3 → 6 duplication included 5 → 10, 6 → 12 and 10 → 20 TMSs. In one case, protein topologies were uncertain as different programs gave discrepant predictions. It could not be concluded with certainty whether a 4 TMS ancestral protein or a 5 TMS ancestral protein duplicated to give an 8 or a 10 TMS protein. Evidence is presented suggesting but not proving that the 2TMS repeat unit in ABC1 porters derived from the two central TMSs of ABC2 porters. These results provide structural information and plausible evolutionary pathways for the appearance of most integral membrane constituents of ABC uptake transport systems.ConclusionsAlmost all integral membrane uptake porters of the ABC superfamily belong to the ABC2 family, previously established for exporters. Most of these proteins can have 5, 6, 10, 12 or 20 TMSs per polypeptide chain. Evolutionary pathways for their appearance are proposed.

Dataset Information

Selecting for Altered Substrate Specificity Reveals the Evolutionary Flexibility of ATP-Binding Cassette Transporters.

Publications

Selecting for Altered Substrate Specificity Reveals the Evolutionary Flexibility of ATP-Binding Cassette Transporters.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets