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J Mol Biol. 1999 Oct 22;293(2):381-99.

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

Author information

1
Institut de Genetique et Microbiologie, Batiment 409, Universite Paris-Sud, 91405, France. holland@igmors.u-psud.fr

Abstract

The approximately 27 kDa ABC-ATPase, an extraordinarily conserved, unique type of ATPase, acts as a machine to fuel the movement across membranes of almost any type of molecule, from large polypeptides to small ions, via many different membrane-spanning proteins. A particular ABC-ATPase must therefore be tailor-made to function in a complex with its cognate membrane protein, forming a transport pathway appropriate for a specific type of molecule, or in the case of some ABC-transporters, several types of molecule. Molecules to be transported recognise their own transporter, bind and switch on the 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 transporter. In this review, we try to identify the common fundamental principles which unite all ABC-transporters, including the basis of specificity for different transported compounds (allocrites), the interactions between the ATPase and membrane domains, activation of the ATPase and the coupling of consequent conformational changes, to the final movement of an allocrite through a given transport pathway. We discuss the so far limited structural information for the intact ABC-transporter complex and the exciting information from the first crystal structure of an ABC-ATPase. Finally, the action of specific transporters, CFTR (Cl- transport), Pgp, MRP and LmrA, all transporting many different drug molecules and HlyB transporting a large protein toxin are discussed.

PMID:
10529352
DOI:
10.1006/jmbi.1999.2993
[Indexed for MEDLINE]

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