User:Lori Wetmore/Sandbox 4
From Proteopedia
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The ATP binding cassette is the most conserved part of an ABC transporter. All ABCs consist of two domains: a RecA-like domain, containing both the Walker A and Walker B motifs, and a helical domain, that contains a unique LSGGQ motif. The two domains are joined by flexible loops, one of which, the Q loop, mediates the interaction between the ABC and the TMD.<ref name="Locher">PMID:18957379</ref> | The ATP binding cassette is the most conserved part of an ABC transporter. All ABCs consist of two domains: a RecA-like domain, containing both the Walker A and Walker B motifs, and a helical domain, that contains a unique LSGGQ motif. The two domains are joined by flexible loops, one of which, the Q loop, mediates the interaction between the ABC and the TMD.<ref name="Locher">PMID:18957379</ref> | ||
| - | ABC transporters function as homodimers. The <scene name='User:Lori_Wetmore/Sandbox_4/Sav1866/8'>two ATP binding sites</scene> of an assembled transporter are at the interfaces of two ABC subunits, where the ATP interacts with the Walker A motif (yellow) on one subunit and the LSGGQ motif (pink) on the other. | + | ABC transporters function as homodimers. The <scene name='User:Lori_Wetmore/Sandbox_4/Sav1866/8'>two ATP binding sites</scene> of an assembled transporter are at the interfaces of two ABC subunits, where the ATP interacts with the Walker A motif (yellow) on one subunit and the LSGGQ motif (pink) on the other. The Walker A motif has the sequence GxxGxGKST, in which the well-conserved <scene name='User:Lori_Wetmore/Sandbox_4/Sav1866/11'>lysine</scene> residue, shown in green, stabilizes the bound ATP by hydrogen bonding with the alpha and gamma phosphates. |
Binding of ATP closes the interface between the NBDs, which in turn draws the cytosolic portion of the TMDs together, exposing the substrate-binding site to the extracellular space. Hydrolysis and release of ATP causes the separation of the NBDs, pushing the cytosolic ends of the transmembrane domains apart. As the cytosolic ends of the NBDs are drawn apart, their extracellular ends come together, making the substrate-binding site inaccessible on the extracellular face of the membrane and accessible to the intracellular face of the membrane. This cycle of ATP binding and hydrolysis fuels both ABC importers and ABC exporters.<ref name="Locher">PMID:18957379</ref> | Binding of ATP closes the interface between the NBDs, which in turn draws the cytosolic portion of the TMDs together, exposing the substrate-binding site to the extracellular space. Hydrolysis and release of ATP causes the separation of the NBDs, pushing the cytosolic ends of the transmembrane domains apart. As the cytosolic ends of the NBDs are drawn apart, their extracellular ends come together, making the substrate-binding site inaccessible on the extracellular face of the membrane and accessible to the intracellular face of the membrane. This cycle of ATP binding and hydrolysis fuels both ABC importers and ABC exporters.<ref name="Locher">PMID:18957379</ref> | ||
Revision as of 20:05, 27 September 2010
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| 2hyd, resolution 3.00Å () | |||||||||
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| Ligands: | , | ||||||||
| Gene: | SAV1866 (Staphylococcus aureus) | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
Background Information
ATP-binding cassette (ABC) transporters are a superfamily of integral membrane proteins that harness the energy of ATP binding and hydrolysis to drive the trans-membrane movement of a variety of small molecules. ABC transporters function as homodimers, in which ATP binding and hydrolysis occurs in two sites that the interface of the nucleotide binding domains (NBD), while the paired transmembrane domains (TMD) facilitate substrate transport. Substrates may be imported or exported, depending upon the structure of the transporter. In ABC importers, which have only been found in prokaryotes, the NBD and TMD are separate polypeptides; however, in the ubiquitous exporters, the NBD and TMD are fused.[1]
ABC transporters are of particular medical interest, as they may contribute to the pathogenicity and drug resistance of pathogenic bacteria and some cancers. [2]
General ABC Structure
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The ATP binding cassette is the most conserved part of an ABC transporter. All ABCs consist of two domains: a RecA-like domain, containing both the Walker A and Walker B motifs, and a helical domain, that contains a unique LSGGQ motif. The two domains are joined by flexible loops, one of which, the Q loop, mediates the interaction between the ABC and the TMD.[3]
ABC transporters function as homodimers. The of an assembled transporter are at the interfaces of two ABC subunits, where the ATP interacts with the Walker A motif (yellow) on one subunit and the LSGGQ motif (pink) on the other. The Walker A motif has the sequence GxxGxGKST, in which the well-conserved residue, shown in green, stabilizes the bound ATP by hydrogen bonding with the alpha and gamma phosphates.
Binding of ATP closes the interface between the NBDs, which in turn draws the cytosolic portion of the TMDs together, exposing the substrate-binding site to the extracellular space. Hydrolysis and release of ATP causes the separation of the NBDs, pushing the cytosolic ends of the transmembrane domains apart. As the cytosolic ends of the NBDs are drawn apart, their extracellular ends come together, making the substrate-binding site inaccessible on the extracellular face of the membrane and accessible to the intracellular face of the membrane. This cycle of ATP binding and hydrolysis fuels both ABC importers and ABC exporters.[3]
ABC Exporters
Despite their diversity in function, ABC exporters maintain relatively strong structural similarities. All of the exporters have twelve (six helices contributed by each subunit) that extend about 25 Å into the cytosol. By examining the of the TMDs, it becomes clear that only the central portion of the TMD is embedded in the membrane (residues are indicated as: Hydrophobic or Polar). The alpha helices contributed by each subunit do not align as parallel bundles; rather, they are considerably .
Type I ABC Importers
Type II ABC Importers
References
- ↑ Davidson AL, Dassa E, Orelle C, Chen J. Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiol Mol Biol Rev. 2008 Jun;72(2):317-64, table of contents. PMID:18535149 doi:10.1128/MMBR.00031-07
- ↑ Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2002 Jan;2(1):48-58. PMID:11902585 doi:10.1038/nrc706
- ↑ 3.0 3.1 Locher KP. Review. Structure and mechanism of ATP-binding cassette transporters. Philos Trans R Soc Lond B Biol Sci. 2009 Jan 27;364(1514):239-45. PMID:18957379 doi:10.1098/rstb.2008.0125
