Editing ABC transporter (section)

=== Mechanism of transport for exporters ===
[[Image:Abc exporter.jpg|thumb|left|Proposed mechanism of transport for ABC exporters. This model was based on structural and biochemical studies on MsbA.]]

ABC exporters have a transport mechanism that is consistent with both the alternating-access model and ATP-switch model. In the apo states of exporters, the conformation is inward-facing and the TMDs and NBDs are relatively far apart to accommodate amphiphilic or hydrophobic substrates. For MsbA, in particular, the size of the chamber is large enough to accommodate the sugar groups from lipopolysaccharides (LPS). As has been suggested by several groups, binding of substrate initiates the transport cycle. The "power stroke", that is, ATP binding that induces NBD dimerization and formation of the ATP sandwich, drives the conformational changes in the TMDs. In MsbA, the sugar head groups are sequestered within the chamber during the "power stroke". The cavity is lined with charged and polar residues that are likely solvated creating an energetically unfavorable environment for hydrophobic substrates and energetically favorable for polar moieties in amphiphilic compounds or sugar groups from LPS. Since the lipid cannot be stable for a long time in the chamber environment, lipid A and other hydrophobic molecules may "flip" into an energetically more favorable position within the outer membrane leaflet. The "flipping" may also be driven by the rigid-body shearing of the TMDs while the hydrophobic tails of the LPS are dragged through the lipid bilayer. Repacking of the helices switches the conformation into an outward-facing state. ATP hydrolysis may widen the periplasmic opening and push the substrate towards the outer leaflet of the lipid bilayer. Hydrolysis of the second ATP molecule and release of P<sub>i</sub> separates the NBDs followed by restoration of the resting state, opening the chamber towards the cytoplasm for another cycle.<ref name=msbaward/><ref name=msbareyes2006/><ref name=higgins/><ref name=msbachang2003/><ref name=dong/><ref name=gutmann2010>{{cite journal | vauthors = Gutmann DA, Ward A, Urbatsch IL, Chang G, van Veen HW | title = Understanding polyspecificity of multidrug ABC transporters: closing in on the gaps in ABCB1 | journal = Trends in Biochemical Sciences | volume = 35 | issue = 1 | pages = 36–42 | date = Jan 2010 | pmid = 19819701 | doi = 10.1016/j.tibs.2009.07.009 | pmc = 4608440 }}</ref>