ABC transporters are fascinating molecular systems that catalyze the vectorial transport of a great variety of substrates across biological membranes. They constitute a large superfamily of primary active transport systems that are present in all kingdoms of life, and play a diversity of physiological roles.

A prominent characteristic of these systems is that they share a highly conserved domain, the ATP binding cassette (ABC), which binds and hydrolyzes ATP. The amino acid sequence of this cassette displays three major conserved motifs: the Walker A and Walker B motifs commonly found in P-loop containing ATPases or GTPases and a specific signature motif known as the linker peptide, the ABC signature motif, or simply the C loop.

The year 2006 marked the 20th anniversary of the identification of the ABC protein superfamily, and the 30th anniversary of the molecular identification of P-glycoprotein (MDR1, ABCB1). The gene of P-glycoprotein was sequenced in 1986 and it turned out to be the first example of the 48 individual transporters that belong to the ABC protein family in humans.

The cellular physiology of prokaryotes (including cellular processes and their regulation) critically relies on ABC systems. Among prokaryotes, ABC proteins segregate into 29 families belonging to three main functional branches of the ABC system (importers, exporters and "other"). They facilitate the import of essential nutrients and the extrusion of toxins, and participate in DNA repair and translation or regulation of gene expression.

In eukaryotes ABC proteins function only as efflux pumps playing multiple and important physiological roles.

As ABC transporters extrude an unusually large set of chemically diverse compounds, they are implicated in multidrug resistance (MDR) and pleiotropic drug resistance (PDR), and may hinder the clinical treatment of microbial infections and human cancers. However, there is accumulating evidence that MDR transporters also have natural physiological roles.

Alicia Ponte-Sucre (2009) in "ABC Transporters in Microorganisms" Published by Caister Academic Press ISBN 978-1-904455-49-3

Further reading: ABC Transporters

Labels: ABC signature motif, active transport systems, ATP binding cassette, P-loop, superfamily, Walker A motif, Walker B motif