Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Structure of an ABC transporter in complex with its binding protein


ATP-binding cassette (ABC) transporter proteins carry diverse substrates across cell membranes1. Whereas clinically relevant ABC exporters are implicated in various diseases or cause multidrug resistance of cancer cells2,3, bacterial ABC importers are essential for the uptake of nutrients4, including rare elements such as molybdenum. A detailed understanding of their mechanisms requires direct visualization at high resolution and in distinct conformations. Our recent structure of the multidrug ABC exporter Sav1866 has revealed an outward-facing conformation of the transmembrane domains coupled to a closed conformation of the nucleotide-binding domains, reflecting the ATP-bound state5. Here we present the 3.1 Å crystal structure of a putative molybdate transporter (ModB2C2) from Archaeoglobus fulgidus in complex with its binding protein (ModA). Twelve transmembrane helices of the ModB subunits provide an inward-facing conformation, with a closed gate near the external membrane boundary. The ATP-hydrolysing ModC subunits reveal a nucleotide-free, open conformation, whereas the attached binding protein aligns the substrate-binding cleft with the entrance to the presumed translocation pathway. Structural comparison of ModB2C2A with Sav1866 suggests a common alternating access and release mechanism, with binding of ATP promoting an outward-facing conformation and dissociation of the hydrolysis products promoting an inward-facing conformation.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Overall structure.
Figure 2: ModB architecture and conserved gate regions.
Figure 3: NBD conformations and interfaces.


  1. 1

    Holland, I. B., Cole, S. P. C., Kuchler, K. & Higgins, C. F. ABC Proteins: From Bacteria to Man (Academic, London, 2003)

    Google Scholar 

  2. 2

    Gottesman, M. M. & Ambudkar, S. V. Overview: ABC transporters and human disease. J. Bioenerg. Biomembr. 33, 453–458 (2001)

    CAS  Article  Google Scholar 

  3. 3

    Gadsby, D. C., Vergani, P. & Csanady, L. The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 440, 477–483 (2006)

    ADS  CAS  Article  Google Scholar 

  4. 4

    Nikaido, H. & Hall, J. A. Overview of bacterial ABC transporters. Methods Enzymol. 292, 3–20 (1998)

    CAS  Article  Google Scholar 

  5. 5

    Dawson, R. J. P. & Locher, K. P. Structure of a bacterial multidrug ABC transporter. Nature 443, 180–185 (2006)

    ADS  CAS  Article  Google Scholar 

  6. 6

    Schneider, E. & Hunke, S. ATP-binding-cassette (ABC) transport systems: Functional and structural aspects of the ATP-hydrolyzing subunits/domains. FEMS Microbiol. Rev. 22, 1–20 (1998)

    CAS  Article  Google Scholar 

  7. 7

    Rech, S., Deppenmeier, U. & Gunsalus, R. P. Regulation of the molybdate transport operon, modABCD, of Escherichia coli in response to molybdate availability. J. Bacteriol. 177, 1023–1029 (1995)

    CAS  Article  Google Scholar 

  8. 8

    Mouncey, N. J., Mitchenall, L. A. & Pau, R. N. Mutational analysis of genes of the mod locus involved in molybdenum transport, homeostasis, and processing in Azotobacter vinelandii. J. Bacteriol. 177, 5294–5302 (1995)

    CAS  Article  Google Scholar 

  9. 9

    Self, W. T., Grunden, A. M., Hasona, A. & Shanmugam, K. T. Molybdate transport. Res. Microbiol. 152, 311–321 (2001)

    CAS  Article  Google Scholar 

  10. 10

    Chen, J., Sharma, S., Quiocho, F. A. & Davidson, A. L. Trapping the transition state of an ATP-binding cassette transporter: Evidence for a concerted mechanism of maltose transport. Proc. Natl Acad. Sci. USA 98, 1525–1530 (2001)

    ADS  CAS  Article  Google Scholar 

  11. 11

    Locher, K. P., Lee, A. T. & Rees, D. C. The E. coli BtuCD structure: a framework for ABC transporter architecture and mechanism. Science 296, 1091–1098 (2002)

    ADS  CAS  Article  Google Scholar 

  12. 12

    Pinkett, H. W., Lee, A. T., Lum, P., Locher, K. P. & Rees, D. C. An inward-facing conformation of a putative metal-chelate-type ABC transporter. Science 315, 373–377 (2007)

    ADS  CAS  Article  Google Scholar 

  13. 13

    Quiocho, F. A. & Ledvina, P. S. Atomic structure and specificity of bacterial periplasmic receptors for active transport and chemotaxis: variation of common themes. Mol. Microbiol. 20, 17–25 (1996)

    CAS  Article  Google Scholar 

  14. 14

    Hu, Y., Rech, S., Gunsalus, R. P. & Rees, D. C. Crystal structure of the molybdate binding protein ModA. Nature Struct. Biol. 4, 703–707 (1997)

    CAS  Article  Google Scholar 

  15. 15

    Lawson, D. M., Williams, C. E., Mitchenall, L. A. & Pau, R. N. Ligand size is a major determinant of specificity in periplasmic oxyanion-binding proteins: the 1.2 A resolution crystal structure of Azotobacter vinelandii ModA. Structure 6, 1529–1539 (1998)

    CAS  Article  Google Scholar 

  16. 16

    Liu, C. E., Liu, P. G., Wolf, A., Lin, E. & Ames, G. F. Both lobes of the soluble receptor of the periplasmic histidine permease, an ABC transporter (traffic ATPase), interact with the membrane-bound complex. Effect of different ligands and consequences for the mechanism of action. J. Biol. Chem. 274, 739–747 (1999)

    CAS  Article  Google Scholar 

  17. 17

    Prossnitz, E. Determination of a region of the HisJ binding protein involved in the recognition of the membrane complex of the histidine transport system of Salmonella typhimurium. J. Biol. Chem. 266, 9673–9677 (1991)

    CAS  PubMed  Google Scholar 

  18. 18

    Sebulsky, M. T., Shilton, B. H., Speziali, C. D. & Heinrichs, D. E. The role of FhuD2 in iron(III)-hydroxamate transport in Staphylococcus aureus. Demonstration that FhuD2 binds iron(III)-hydroxamates but with minimal conformational change and implication of mutations on transport. J. Biol. Chem. 278, 49890–49900 (2003)

    CAS  Article  Google Scholar 

  19. 19

    Jones, P. M. & George, A. M. The ABC transporter structure and mechanism: perspectives on recent research. Cell. Mol. Life Sci. 61, 682–699 (2004)

    CAS  Article  Google Scholar 

  20. 20

    Higgins, C. F. & Linton, K. J. The ATP switch model for ABC transporters. Nature Struct. Mol. Biol. 11, 918–926 (2004)

    CAS  Article  Google Scholar 

  21. 21

    Hopfner, K. P. et al. Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily. Cell 101, 789–800 (2000)

    CAS  Article  Google Scholar 

  22. 22

    Smith, P. C. et al. ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer. Mol. Cell 10, 139–149 (2002)

    CAS  Article  Google Scholar 

  23. 23

    Chen, J., Lu, G., Lin, J., Davidson, A. L. & Quiocho, F. A. A tweezers-like motion of the ATP-binding cassette dimer in an ABC transport cycle. Mol. Cell 12, 651–661 (2003)

    CAS  Article  Google Scholar 

  24. 24

    Mannering, D. E., Sharma, S. & Davidson, A. L. Demonstration of conformational changes associated with activation of the maltose transport complex. J. Biol. Chem. 276, 12362–12368 (2001)

    CAS  Article  Google Scholar 

  25. 25

    Mourez, M., Hofnung, N. & Dassa, E. Subunit interactions in ABC transporters: a conserved sequence in hydrophobic membrane proteins of periplasmic permeases defines an important site of interaction with the ATPase subunits. EMBO J. 16, 3066–3077 (1997)

    CAS  Article  Google Scholar 

  26. 26

    Loo, T. W. & Clarke, D. M. Recent progress in understanding the mechanism of P-glycoprotein-mediated drug efflux. J. Membr. Biol. 206, 173–185 (2005)

    CAS  Article  Google Scholar 

  27. 27

    Davidson, A. L. Mechanism of coupling of transport to hydrolysis in bacterial ATP-binding cassette transporters. J. Bacteriol. 184, 1225–1233 (2002)

    CAS  Article  Google Scholar 

  28. 28

    Sauna, Z. E. & Ambudkar, S. V. Evidence for a requirement for ATP hydrolysis at two distinct steps during a single turnover of the catalytic cycle of human P-glycoprotein. Proc. Natl Acad. Sci. USA 97, 2515–2520 (2000)

    ADS  CAS  Article  Google Scholar 

  29. 29

    Patzlaff, J. S., van der Heide, T. & Poolman, B. The ATP/Substrate stoichiometry of the ATP-binding cassette (ABC) transporter OpuA. J. Biol. Chem. 278, 29546–29551 (2003)

    CAS  Article  Google Scholar 

  30. 30

    Janas, E. et al. The ATP hydrolysis cycle of the nucleotide-binding domain of the mitochondrial ATP-binding cassette transporter Mdl1p. J. Biol. Chem. 278, 26862–26869 (2003)

    CAS  Article  Google Scholar 

Download references


We thank C. Schulze-Briese, E. Pohl and T. Tomizaki for assistance with synchrotron data collection, B. Blattmann for assistance with initial crystallization screening and J. P. Rosenbusch for discussions. This work was supported by the Roche Research Fund, the National Center for Competence in Research (NCCR) Structural Biology Zurich, and the Swiss National Science Foundation.

Coordinates and structure factors for ModA with bound MoO4, ModA with bound WO4, and for the ModB2C2A complex have been deposited in the Protein Data Bank with accession codes 2ONR, 2ONS, and 2ONK, respectively.

Author information



Corresponding author

Correspondence to Kaspar P. Locher.

Ethics declarations

Competing interests

Coordinates and structure factors for ModA with bound MoO4, ModA with bound WO4, and for the ModB2C2A complex have been deposited in the Protein Data Bank with accession codes 2ONR, 2ONS, and 2ONK, respectively. Reprints and permissions information is available at The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Methods, Supplementary Tables S1-S2, Supplementary Figures S1-S5 and additional references. (PDF 1040 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hollenstein, K., Frei, D. & Locher, K. Structure of an ABC transporter in complex with its binding protein. Nature 446, 213–216 (2007).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing