Ib. Holland et Ma. Blight, ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules organisms from bacteria to humans, J MOL BIOL, 293(2), 1999, pp. 381-399
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.