ATP-dependent transport systems in bacteria and humans: relevance to cystic fibrosis and multidrug resistance.
The prokaryotic permeases are members of a superfamily of membrane transporters called traffic ATPases, which includes the medically important eukaryotic multidrug resistance (MDR) protein and cystic fibrosis transmembrane regulator (CFTR). Members of this superfamily have extensive sequence and structural similarity, in particular in an ATP-binding motif, and are believed to use ATP to energize translocation of substrates across biological membranes. The prokaryotic histidine permease is well-characterized and serves as a convenient model system. In this review, we highlight some of the biochemical and molecular biological approaches used to study the functional and architectural organization of this permease and relate the results of these approaches to what is known about other traffic ATPases. We have identified specific regions that we believe critical for the function of the histidine permease and propose that the corresponding regions in the eukaryotic traffic ATPases are also important for their function. In light of the fact that CFTR (and possibly the MDR protein) is an ion channel, we compare the properties of channels and transporters; in addition, we discuss the possibility that other members of the traffic ATPases may also have channel-like activity.
Doige
C A
CA
Department of Molecular and Cell Biology, University of California at Berkeley 94720.
Ames
G F
GF
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D026923:Amino Acid Transport Systems, Basic; D001419:Bacteria / Q000378:metabolism*; D001426:Bacterial Proteins; D001693:Biological Transport, Active; D003550:Cystic Fibrosis / Q000378:metabolism*; D004351:Drug Resistance; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008969:Molecular Sequence Data
D018528:ATP-Binding Cassette Transporters; D026923:Amino Acid Transport Systems, Basic; D001426:Bacterial Proteins; D007473:Ion Channels; D026901:Membrane Transport Proteins; C043828:histidine permease, Bacteria; D000255:Adenosine Triphosphate