ABC proteins in evolution

Abstract

ATP-binding cassette (ABC) proteins play diverse roles in all living organisms, making them an attractive model for evolution. Early evolution of ancestral unicellular organisms entailed the acquisition of at least three types of ABC proteins: type 1 ABC proteins to import nutrients, and type 2 and 3 ABC proteins to generate the outer cell membrane by flopping and loading lipids onto acceptors, respectively. To export various toxic lipophilic compounds, cells evolutionarily acquired a fourth type of ABC protein. This suggests that ABC proteins may have played an important role in evolution, especially when life became terrestrial, protecting plants and animals from water loss and pathogen infection. ABC proteins are also assumed to have accelerated the evolution of vertebrates by allowing cholesterol to function for intramembrane signaling. In this review, we discuss the roles of ABC proteins in the evolution of bacteria, plants, and animals.

Multidrug Resistance in Mammals and Fungi—From MDR to PDR: A Rocky Road from Atomic Structures to Transport Mechanisms

“…All three share rather broad and partially overlapping drug specificity [14,111]. Most substrates of ABCB1 and ABCG2 are cationic hydrophobic compounds [112], which may probably be expelled directly from the lipid phase as originally proposed by the "hydrophobic vacuum cleaner" model [105,113,114] or from the outer membrane leaflet by a floppase-like function [5,14,19,109,111,115,116]. A similar mechanism has been proposed in ABCA1 for the cholesterol loading of apolipoprotein A-I (apoA-I) [5,116,117].…”

“…Substrates shift into the upper cavity and are released by the subsequent opening of the ECL lid (4). ATP hydrolysis at one NBD site may be enough to reset the catalytic cycle and to convert the transporter molecule into the inward-facing drug-recognizing state (5). The structures show NBDs (green), elbow helix (pink), TMDs (yellow), ICL (orange), ECL (purple), phenylalanine clamp (blue hexagon), valve (red), substrates (cyan) and inhibitors (red).…”

“…The ATP-binding cassette (ABC) transporter family is one of the largest protein superfamilies present in all living organisms, from prokaryotes to eukaryotes [ 1 , 2 , 3 , 4 , 5 ]. ABC transporters can operate as exporters or importers in an ATP-dependent manner, and mediate the membrane translocation of bewildering substrate spectra against concentration gradients [ 6 , 7 , 8 ].…”

“…Most substrates of ABCB1 and ABCG2 are cationic hydrophobic compounds [ 112 ], which may probably be expelled directly from the lipid phase as originally proposed by the “hydrophobic vacuum cleaner” model [ 105 , 113 , 114 ] or from the outer membrane leaflet by a floppase-like function [ 5 , 14 , 19 , 109 , 111 , 115 , 116 ]. A similar mechanism has been proposed in ABCA1 for the cholesterol loading of apolipoprotein A-I (apoA-I) [ 5 , 116 , 117 ]. P-gp, MRP1 and ABCG2 are normally residing in the plasma membrane of epithelial organ linings (such as liver, intestine, blood–brain barrier, placenta and mammary epithelium) [ 118 , 119 ].…”

The incredible diversity of structures and functions of ABC transporters

“…Interestingly, this task turns out to be challenging, especially given the context of emerging new functional information, often in conflict with ‘established’ knowledge [32]. Here, genuine attempts to reclassify ABC transporters based on their TMD folds [33] or on evolutionary relationships obtained from the combination of natural and experimentally produced sequence variations are proposed [34,35]. Hopefully, this will stimulate debate, leading to the refinement of new proposals.…”