ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules organisms from bacteria to humans

The approximately 27 kDa ABC-ATPase, an extraordinarily conserved, unique t ype of ATPase, acts-as a machine to fuel the movement across membranes of a lmost any type of molecule, from large polypeptides to small ions, via many different membrane-spanning proteins. A particular ABC-ATPase must therefo re be tailor-made to function in a complex with its cognate membrane protei n, forming a transport pathway appropriate for a specific type of molecule, or in the case of some ABC-transporters, several types of molecule. Molecu les to be transported recognise their own transporter, bind and switch on t he ATPase, which in turn activates or opens the transport pathway. ABC-dependent transport can be inwards across the membrane, or outwards to the cell exterior, and the ABC-ATPase can fuel. transport through pathways which may involve a classical channel (CFTR), a "gateway" mechanism through a proteinacious chamber spanning the bilayer, or conceivably via a pathway at the protein-lipid interface of the outside of the membrane domain, This may be the case for drugs transported by Pgp, a multidrug resistance trans porter. In this review, we try to identify the common fundamental principles which unite all ABC-transporters, including the basis of specificity for differen t transported compounds (allocrites), the interactions between the ATPase a nd membrane domains, activation of the ATPase and the coupling of consequen t conformational changes, to the final movement of an allocrite through a g iven transport pathway. We discuss the so far limited structural informatio n for the intact ABC-transporter complex and the exciting information from the first crystal structure of an ABC-ATPase. Finally, the action of specif ic transporters, CFTR (Cl- transport), Pgp, MRP and LmrA, all transporting many different drug molecules and HlyB transporting a large protein toxin a re discussed. (C) 1999 Academic Press.