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Crystal structure of the aquaglyceroporin PfAQP from the malarial parasite Plasmodium falciparum

Nature Structural & Molecular Biology volume 15, pages 619–625 (2008)Cite this article

Abstract

The 2.05-Å resolution structure of the aquaglyceroporin from the malarial parasite Plasmodium falciparum (PfAQP), a protein important in the parasite's life cycle, has been solved. The structure provides key evidence for the basis of water versus glycerol selectivity in aquaporin family members. Unlike its closest homolog of known structure, GlpF, the channel conducts both glycerol and water at high rates, framing the question of what determines high water conductance in aquaporin channels. The universally conserved arginine in the selectivity filter is constrained by only two hydrogen bonds in GlpF, whereas there are three in all water-selective aquaporins and in PfAQP. The decreased cost of dehydrating the triply-satisfied arginine cation may provide the basis for high water conductance. The two Asn-Pro-Ala (NPA) regions of PfAQP, which bear rare substitutions to Asn-Leu-Ala (NLA) and Asn-Pro-Ser (NPS), participate in preserving the orientation of the selectivity filter asparagines in the center of the channel.

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Figure 1: Channel architecture.
Figure 2: Details of the PfAQP conduction channel.
Figure 3: Selectivity in aquaporin channels.
Figure 4: Water and glycerol conduction assay.
Figure 5: Alterations to the conserved NPA motif in PfAQP.

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References

  1. Hansen, M., Kun, J.F., Schultz, J.E. & Beitz, E. A single, bi-functional aquaglyceroporin in blood-stage Plasmodium falciparum malaria parasites. J. Biol. Chem. 277, 4874–4882 (2002).

    Article  CAS  Google Scholar 

  2. Vial, H.J. & Ancelin, M.L. Malarial lipids. An overview. Subcell. Biochem. 18, 259–306 (1992).

    Article  CAS  Google Scholar 

  3. Vial, H.J., Ancelin, M.L., Thuet, M.J. & Philippot, J.R. Phospholipid metabolism in Plasmodium-infected erythrocytes: guidelines for further studies using radioactive precursor incorporation. Parasitology 98, 351–357 (1989).

    Article  CAS  Google Scholar 

  4. Beitz, E., Pavlovic-Djuranovic, S., Yasui, M., Agre, P. & Schultz, J.E. Molecular dissection of water and glycerol permeability of the aquaglyceroporin from Plasmodium falciparum by mutational analysis. Proc. Natl. Acad. Sci. USA 101, 1153–1158 (2004).

    Article  CAS  Google Scholar 

  5. Promeneur, D. et al. Aquaglyceroporin PbAQP during intraerythrocytic development of the malaria parasite Plasmodium berghei. Proc. Natl. Acad. Sci. USA 104, 2211–2216 (2007).

    Article  CAS  Google Scholar 

  6. Liu, Y. et al. Aquaporin 9 is the major pathway for glycerol uptake by mouse erythrocytes, with implications for malarial virulence. Proc. Natl. Acad. Sci. USA 104, 12560–12564 (2007).

    Article  CAS  Google Scholar 

  7. Gardner, M.J. et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419, 498–511 (2002).

    Article  CAS  Google Scholar 

  8. Jayaraj, S., Reid, R. & Santi, D.V. GeMS: an advanced software package for designing synthetic genes. Nucleic Acids Res. 33, 3011–3016 (2005).

    Article  CAS  Google Scholar 

  9. Fu, D. et al. Structure of a glycerol-conducting channel and the basis for its selectivity. Science 290, 481–486 (2000).

    Article  CAS  Google Scholar 

  10. Sui, H., Han, B.G., Lee, J.K., Walian, P. & Jap, B.K. Structural basis of water-specific transport through the AQP1 water channel. Nature 414, 872–878 (2001).

    Article  CAS  Google Scholar 

  11. Fujiyoshi, Y. et al. Structure and function of water channels. Curr. Opin. Struct. Biol. 12, 509–515 (2002).

    Article  CAS  Google Scholar 

  12. Kozono, D. et al. Functional expression and characterization of an archaeal aquaporin. AqpM from Methanothermobacter marburgensis. J. Biol. Chem. 278, 10649–10656 (2003).

    Article  CAS  Google Scholar 

  13. Fu, D., Libson, A. & Stroud, R. The structure of GlpF, a glycerol conducting channel. Novartis Found. Symp. 245, 51–61; Discussion 61–5, 165–8 (2002).

    CAS  PubMed  Google Scholar 

  14. Wang, Y., Schulten, K. & Tajkhorshid, E. What makes an aquaporin a glycerol channel? A comparative study of AqpZ and GlpF. Structure 13, 1107–1118 (2005).

    Article  CAS  Google Scholar 

  15. Jensen, M.O., Park, S., Tajkhorshid, E. & Schulten, K. Energetics of glycerol conduction through aquaglyceroporin GlpF. Proc. Natl. Acad. Sci. USA 99, 6731–6736 (2002).

    Article  CAS  Google Scholar 

  16. Lee, J.K. et al. Structural basis for conductance by the archaeal aquaporin AqpM at 1.68 Å. Proc. Natl. Acad. Sci. USA 102, 18932–18937 (2005).

    Article  CAS  Google Scholar 

  17. Savage, D.F., Egea, P.F., Robles-Colmenares, Y., O'Connell, J.D. III & Stroud, R.M. Architecture and selectivity in aquaporins: 2.5 X-ray structure of aquaporin Z. PLoS Biol. 1, e72 (2003).

    Article  Google Scholar 

  18. Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307–326 (1997).

    Article  CAS  Google Scholar 

  19. McCoy, A.J., Grosse-Kunstleve, R.W., Storoni, L.C. & Read, R.J. Likelihood-enhanced fast translation functions. Acta Crystallogr. D Biol. Crystallogr. 61, 458–464 (2005).

    Article  Google Scholar 

  20. Perrakis, A., Morris, R. & Lamzin, V.S. Automated protein model building combined with iterative structure refinement. Nat. Struct. Biol. 6, 458–463 (1999).

    Article  CAS  Google Scholar 

  21. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).

    Article  Google Scholar 

  22. Winn, M.D., Isupov, M.N. & Murshudov, G.N. Use of TLS parameters to model anisotropic displacements in macromolecular refinement. Acta Crystallogr. D Biol. Crystallogr. 57, 122–133 (2001).

    Article  CAS  Google Scholar 

  23. Murshudov, G.N., Vagin, A.A. & Dodson, E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53, 240–255 (1997).

    Article  CAS  Google Scholar 

  24. Collaborative Computational Project, Number 4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D Biol. Crystallogr. 50, 760–763 (1994).

  25. Davis, I.W. et al. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res. 35, W375–W383 (2007).

    Article  Google Scholar 

  26. Smart, O.S., Goodfellow, J.M. & Wallace, B.A. The pore dimensions of gramicidin A. Biophys. J. 65, 2455–2460 (1993).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Research was supported by the US National Institutes of Health (NIH) grant GM24485 to R.M.S. and by the NIH Roadmap center grant P50 GM073210. The authors thank the reviewers for their helpful suggestions. The authors thank F.A. Hays, P. Egea, J. Lee and D. Savage in the Stroud laboratory for helpful advice throughout the project and with preparation of the manuscript. The authors thank T.P. Kearney III and M. Miller for advice on the manuscript. We thank J. Holton for his assistance at the Advanced Light Source (ALS) beamline 8.3.1, supported by NIH grant GM074929 (R.M.S.).

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  1. Shahram Khademi

    Present address: Present address: Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, 4-610 Bowen Science Building, Iowa City, Iowa 52242-1109, USA.,

Authors and Affiliations

  1. Department of Chemistry and Chemical Biology Graduate Program, and Department of Biochemistry and Biophysics, Genentech Hall, School of Medicine, University of California in San Francisco, 600 16th Street, San Francisco, 94158-2517, California, USA

    Zachary E R Newby, Joseph O'Connell III, Yaneth Robles-Colmenares, Shahram Khademi, Larry J Miercke & Robert M Stroud

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Contributions

Z.E.R.N., J.O. III, Y.R.-C. and S.K. carried out experiments; Z.E.R.N. collected diffraction data and determined the structure; R.M.S. and L.J.M. supervised the research; Z.E.R.N. and R.M.S. wrote the manuscript.

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Correspondence to Robert M Stroud.

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Newby, Z., O'Connell III, J., Robles-Colmenares, Y. et al. Crystal structure of the aquaglyceroporin PfAQP from the malarial parasite Plasmodium falciparum. Nat Struct Mol Biol 15, 619–625 (2008). https://doi.org/10.1038/nsmb.1431

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