#ABC TRANSPORTER PROTEIN FULL#

It is generally believed that during a single transport cycle, two molecules of ATP are consumed, which is consistent with positive cooperativity observed for ATP hydrolysis in several ABC transporters ( Senior & Bhagat 1998). When ATP is bound, the interface closes and the nucleotides are sandwiched between the NBDs ( Chen et al. In the absence of a nucleotide, there is a gap at the domain interface, with water being able to access the nucleotide-binding sites. This arrangement generates two ATP binding and hydrolysis sites between the P-loops of one NBD and the LSGGQ motif of the other, hence the name ‘head-to-tail’ ( figure 2 a).

#ABC TRANSPORTER PROTEIN FULL#

In full transporters, the two NBDs assemble such that these conserved motifs are exposed at the shared interface in a head-to-tail arrangement ( figure 2). The most important of these are the P-loops (Walker-A motifs), located in the RecA-like sub-domain, and the LSGGQ motif (denoting the amino acid sequence in single letter code), located in the helical sub-domain. There are several conserved sequence motifs in the NBDs, all with specific functions ( Jones & George 2004). NBDs contain two sub-domains, one resembling the functionally unrelated RecA protein, and another that has been dubbed the ‘helical sub-domain’. The NBD is the conserved domain of this protein family, and may be regarded as a common engine attached to diverse TMDs. A conserved coupling mechanism for ABC transporters In particular, it appears that a conserved coupling mechanism may allow both ABC importers and exporters to convert ATP binding and hydrolysis to conformational changes that facilitate active transport ( Dawson et al. The advent of high-resolution structures of full length ABC transporters in recent years have led to a more unified picture ( Hollenstein et al. Since the clustering of prokaryotic and eukaryotic ABC transporters into one protein family ( Higgins 1992), various and sometimes contradictory mechanistic models have been presented and discussed. Considerable efforts have been directed at understanding the detailed mechanism of ABC transporters, which is in part motivated by the fact that there are several clinically relevant examples ( Gottesman & Ambudkar 2001). Note that importers have, to this date, only been found in prokaryotes, whereas exporter-type ABC transporters are expressed ubiquitously in all kingdoms of life. The basic domain architecture and schematic mechanism are shown in figure 1. In both cases, ATP hydrolysis is catalysed by a pair of cytoplasmic ABCs (also termed nucleotide-binding domains, NBDs), whereas the translocation of the substrate is facilitated by a pair of transmembrane domains (TMDs). They convert the energy gained from ATP hydrolysis into trans-bilayer movement of substrates either into the cytoplasm (import) or out of the cytoplasm (export). ATP-binding cassette (ABC) transporters are a large superfamily of membrane proteins with diverse functions ( Holland et al.

Abc transporter protein