THE GENETICS OF ABC TRANSPORTER1.0 INTRODUCTIONThe transport of organic and inorganic molecules across cellular membranes is vital to allforms of life, as it allows cells to maintain an off equilibrium condition. In Escherichia coli,for example, ~10% of the entire genome is dedicated to membrane-bound and solubleproteins involved in transport processes (Blattner et al., 1997). On the timescale relevant forcellular metabolism, the lipid bilayer represents a formidable barrier for most charged andpolar molecules while allowing for the passage of hydrophobic organic compounds bypassive diffusion (Paula et al., 1996). Transport against a chemical gradient (e.g. import ofnutrients) requires a source of free energy, either provided by the potential energy of anexisting chemical gradient or a coupled enzymatic reaction. Transporters that are driven bythe chemical gradient of a “helper” molecule are referred to as secondary transporters, whiletransporters that generate the driving force by an enzymatic reaction with a “high energy”molecule (mostly ATP) are called primary transporters (Saier et al., 2014).Transporters that use ATP hydrolysis to pump molecules across the membrane are referred toas transport ATPases, a large superfamily that includes the rotarymotor F-, A-, and V-ATPases, the P-type ATPases and the ABC transporters (Pedersen 2008). While transportsubstrates of the rotary motor and P-type ATPases are, with few exceptions, limited toprotons or metal ions, ABC transporters cover a wide spectrum of substrates, from smallinorganic and organic molecules, such as amino acids, sugars, nucleosides, vitamins andmetal clusters to larger organic compounds, including peptides, lipid molecules,oligonucleotides and polysaccharides. Over the past decade, several moderate to- highresolution crystal structures have been solved for a variety of ABC transporters from micro-organisms and higher eukaryotes, including mammals. The structural data, together with
sophisticated biochemical and biophysical studies, have provided a wealth of information onthe catalytic mechanism of ATP hydrolysis-driven transport. This mini-review gives a briefoverview of the current understanding of the structure and mechanism of ABC transportersand what some of the remaining and emerging questions are