Editing ABC transporter (section)

== ABC importers ==
Most ABC transporters that mediate the uptake of nutrients and other molecules in bacteria rely on a high-affinity solute binding protein (BP). BPs are soluble proteins located in the periplasmic space between the inner and outer membranes of [[gram-negative bacteria]]. [[Gram-positive]] microorganisms lack a [[periplasm]] such that their binding protein is often a [[lipoprotein]] bound to the external face of the [[cell membrane]]. Some gram-positive bacteria have BPs fused to the transmembrane domain of the transporter itself.<ref name=davidson/> The first successful [[x-ray crystallography|x-ray crystal]] structure of an intact ABC importer is the [[molybdenum]] transporter (ModBC-A) from ''Archaeoglobus fulgidus''.<ref name=modb/> Atomic-resolution structures of three other bacterial importers, ''E. coli'' BtuCD,<ref name=btucd/> ''E. coli'' [[maltose]] transporter (MalFGK<sub>2</sub>-E),<ref name=malkoldham/> and the putative metal-chelate transporter of ''Haemophilus influenzae'', HI1470/1,<ref name=hi1471/> have also been determined. The structures provided detailed pictures of the interaction of the transmembrane and ABC domains as well as revealed two different conformations with an opening in two opposite directions. Another common feature of importers is that each NBD is bound to one TMD primarily through a short cytoplasmic helix of the TMD, the "coupling helix". This portion of the EAA loop docks in a surface cleft formed between the RecA-like and helical ABC subdomains and lies approximately parallel to the membrane bilayer.<ref name=oldham2008/>

=== Large ABC importers ===
The BtuCD and HI1470/1 are classified as large (Type II) ABC importers. The transmembrane subunit of the vitamin B<sub>12</sub> importer, BtuCD, contains 10 TM helices and the functional unit consists of two copies each of the nucleotide binding domain (NBD) and transmembrane domain (TMD). The TMD and NBD interact with one another via the cytoplasmic loop between two TM helices and the Q loop in the ABC. In the absence of nucleotide, the two ABC domains are folded and the dimer interface is open. A comparison of the structures with (BtuCDF) and without (BtuCD) binding protein reveals that BtuCD has an opening that faces the periplasm whereas in BtuCDF, the outward-facing conformation is closed to both sides of the membrane. The structures of BtuCD and the BtuCD homolog, HI1470/1, represent two different conformational states of an ABC transporter. The predicted translocation pathway in BtuCD is open to the periplasm and closed at the cytoplasmic side of the membrane while that of HI1470/1 faces the opposite direction and open only to the cytoplasm. The difference in the structures is a 9° twist of one TM subunit relative to the other.<ref name=davidson/><ref name=rees/><ref name=oldham2008/>

=== Small ABC importers ===
Structures of the ModBC-A and MalFGK<sub>2</sub>-E, which are in complex with their binding protein, correspond to small (Type I) ABC importers. The TMDs of ModBC-A and MalFGK<sub>2</sub>-E have only six helices per subunit. The homodimer of ModBC-A is in a conformation in which the TM subunits (ModB) orient in an inverted V-shape with a cavity accessible to the cytoplasm. The ABC subunits (ModC), on the other hand, are arranged in an open, nucleotide-free conformation, in which the P-loop of one subunit faces but is detached from the LSGGQ motif of the other. The binding protein ModA is in a closed conformation with substrate bound in a cleft between its two lobes and attached to the extracellular loops of ModB, wherein the substrate is sitting directly above the closed entrance of the transporter. The MalFGK<sub>2</sub>-E structure resembles the catalytic [[transition state]] for ATP hydrolysis. It is in a closed conformation where it contains two ATP molecules, sandwiched between the Walker A and B motifs of one subunit and the LSGGQ motif of the other subunit. The maltose binding protein (MBP or MalE) is docked on the periplasmic side of the TM subunits (MalF and MalG) and a large, occluded cavity can be found at the interface of MalF and MalG. The arrangement of the TM helices is in a conformation that is closed toward the cytoplasm but with an opening that faces outward. The structure suggests a possibility that MBP may stimulate the [[ATPase]] activity of the transporter upon binding.<ref name=davidson/><ref name=rees/><ref name=oldham2008/>

=== Mechanism of transport for importers ===
[[Image:Abc importer.jpg|thumb|Proposed mechanism of transport for ABC importers. This alternating-access model was based on the crystal structures of ModBC-A<ref name=modb/> and HI1470/1.<ref name=hi1471/>]]

The mechanism of transport for importers supports the alternating-access model. The resting state of importers is inward-facing, where the nucleotide binding domain (NBD) dimer interface is held open by the TMDs and facing outward but occluded from the cytoplasm. Upon docking of the closed, substrate-loaded binding protein towards the periplasmic side of the transmembrane domains, ATP binds and the NBD dimer closes. This switches the resting state of transporter into an outward-facing conformation, in which the TMDs have reoriented to receive substrate from the binding protein. After hydrolysis of ATP, the NBD dimer opens and substrate is released into the cytoplasm. Release of ADP and P<sub>i</sub> reverts the transporter into its resting state. The only inconsistency of this mechanism to the ATP-switch model is that the conformation in its resting, nucleotide-free state is different from the expected outward-facing conformation. Although that is the case, the key point is that the NBD does not dimerize unless ATP and binding protein is bound to the transporter.<ref name=davidson/><ref name=davidsonchen/><ref name=rees/><ref name=higgins/><ref name=oldham2008/>