抄録
The ATP-Binding Cassette (ABC) transporters, forming one of the largest known protein families, are involved in the ATP-dependent transport of a great variety of compounds, ranging from inorganic anions to large polypeptides. The ABC transporters are generally built from combinations of two conservative Nucleotide Binding Domains (NBD) and two characteristic Membrane Spanning Domains (MSD). Recent crystallographic studies of ABC transporters suggested that two ATP binding pockets (ABP1 and ABP2) are formed by the Walker A and B motifs from one NBD and the signature sequence from the partner NBD. Two NBDs are dimerized in a head-to-tail configuration upon ATP binding to ABP1 and ABP2 buried at the dimer interface. Sequential ATP-hydrolysis at ABPs provides energy for breaking the NBD dimer. The NBD conformational changes associated with the ATP-hydrolysis cycle are supposed to induce conformational changes in MSDs. Thus NBD converts the ATP-hydrolysis energy to mechanical force for transporting the substrate molecules through cellular or intracellular membranes. However the mechanism of the "NBD engine" is still unclear in spite of its strong physiological impacts. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is the only one member of the ABC transporter family which functions as a channel. In CFTR, the NBD engine is thought to drive the channel gate. The channel gating function of CFTR gives us an advantage to observe behaviors of the NBD engine on real-time base. We will discuss the mechanism of the NBD engine with using the CFTR channel gating as a model of the common transport mechanism in ABC transporter family. [J Physiol Sci. 2007;57 Suppl:S62]
