Journal of Bioenergetics and Biomembranes

, Volume 39, Issue 5–6, pp 499–505

Building an understanding of cystic fibrosis on the foundation of ABC transporter structures

Transport ATPases: Structure, Mechanism and Relevance to Multiple Diseases


Cystic fibrosis (CF) is a fatal disease affecting the lungs and digestive system by impairment of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). While over 1000 mutations in CFTR have been associated with CF, the majority of cases are linked to the deletion of phenylalanine 508 (ΔF508). F508 is located in the first nucleotide binding domain (NBD1) of CFTR. This mutation is sufficient to impair the trafficking of CFTR to the plasma membrane and, thus, its function. As an ABC transporter, recent structural data from the family provide a framework on which to consider the effect of the ΔF508 mutation on CFTR. There are fifty-seven known structures of ABC transporters and domains thereof. Only six of these structures are of the intact transporters. In addition, modern bioinformatic tools provide a wealth of sequence and structural information on the family. We will review the structural information from the RCSB structure repository and sequence databases of the ABC transporters. The available structural information was used to construct a model for CFTR based on the ABC transporter homologue, Sav1866, and provide a context for understanding the molecular pathology of Cystic Fibrosis.


ABC transporters CFTR Cystic fibrosis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Baker JM, Hudson RP, Kanelis V, Choy WY, Thibodeau PH et al (2007) Nat Struct Mol Biol 14(8):738–745CrossRefGoogle Scholar
  2. Biemans-Oldehinkel E, Doeven MK, Poolman B (2006) FEBS Lett 580(4):1023–1035CrossRefGoogle Scholar
  3. Chang G, Roth CB (2001) Science 293(5536):1793–1800CrossRefGoogle Scholar
  4. Chang G, Roth CB, Reyes CL, Pornillos O, Chen YJ et al (2006) Science 314(5807):1875CrossRefGoogle Scholar
  5. Cheng SH, Gregory RJ, Marshall J, Paul S, Souza DW et al (1990) Cell 63(4):827–834CrossRefGoogle Scholar
  6. Cotten JF, Ostedgaard LS, Carson MR, Welsh MJ (1996) J Biol Chem 271(35):21279–21284CrossRefGoogle Scholar
  7. Dassa E, Hofnung M (1985) Ann Inst Pasteur Microbiol 136A(3):281–288CrossRefGoogle Scholar
  8. Dawson RJ, Locher KP (2006) Nature 443(7108):180–185CrossRefGoogle Scholar
  9. Dawson RJ, Hollenstein K, Locher KP (2007) Mol Microbiol 65(2):250–257CrossRefGoogle Scholar
  10. DeCarvalho AC, Gansheroff LJ, Teem JL (2002) J Biol Chem 277(39):35896–35905CrossRefGoogle Scholar
  11. Doige CA, Ames GF (1993) Annu Rev Microbiol 47:291–319CrossRefGoogle Scholar
  12. Dork T, Wulbrand U, Richter T, Neumann T, Wolfes H et al (1991) Hum Genet 87(4):441–446CrossRefGoogle Scholar
  13. Fetsch EE, Davidson AL (2002) Proc Natl Acad Sci U S A 99(15):9685–9690CrossRefGoogle Scholar
  14. Higgins CF (1992) Annu Rev Cell Biol 8:67–113CrossRefGoogle Scholar
  15. Hollenstein K, Frei DC, Locher KP (2007) Nature 446(7132):213–216CrossRefGoogle Scholar
  16. Hopfner KP, Karcher A, Shin DS, Craig L, Arthur LM et al (2000) Cell 101(7):789–800CrossRefGoogle Scholar
  17. Hung LW, Wang IX, Nikaido K, Liu PQ, Ames GF et al (1998) Nature 396(6712):703–707CrossRefGoogle Scholar
  18. Jones PM, George AM (1999) FEMS Microbiol Lett 179(2):187–202CrossRefGoogle Scholar
  19. Jones PM, George AM (2004) Cell Mol Life Sci 61(6):682–699CrossRefGoogle Scholar
  20. Leslie EM, Deeley RG, Cole SP (2001) Toxicology 167(1):3–23CrossRefGoogle Scholar
  21. Lewis HA, Buchanan SG, Burley SK, Conners K, Dickey M et al (2004) EMBO J 23(2):282–293CrossRefGoogle Scholar
  22. Lewis HA, Zhao X, Wang C, Sauder JM, Rooney I et al (2005) J Biol Chem 280(2):1346–1353CrossRefGoogle Scholar
  23. Locher KP, Lee AT, Rees DC (2002) Science 296(5570):1091–1098CrossRefGoogle Scholar
  24. Loo TW, Bartlett MC, Clarke DM (2002) J Biol Chem 277(44):41303–41306CrossRefGoogle Scholar
  25. Lukacs GL, Mohamed A, Kartner N, Chang XB, Riordan JR et al (1994) EMBO J 13(24):6076–6086Google Scholar
  26. Matthews BW (2007) Protein Sci 16(6):1013–1016CrossRefGoogle Scholar
  27. Moody JE, Millen L, Binns D, Hunt JF, Thomas PJ (2002) J Biol Chem 277(24):21111–21114CrossRefGoogle Scholar
  28. Murzin AG, Brenner SE, Hubbard T, Chothia C (1995) J Mol Biol 247(4):536–540CrossRefGoogle Scholar
  29. Nikaido K, Liu PQ, Ames GF (1997) J Biol Chem 272(44):27745–27752CrossRefGoogle Scholar
  30. Orengo CA, Michie AD, Jones S, Jones DT, Swindells MB et al (1997) Structure 5(8):1093–1108CrossRefGoogle Scholar
  31. Reyes CL, Chang G (2005) Science 308(5724):1028–1031CrossRefGoogle Scholar
  32. Saraste M, Sibbald PR, Wittinghofer A (1990) Trends Biochem Sci 15(11):430–434CrossRefGoogle Scholar
  33. Saurin W, Dassa E (1994) Protein Sci 3(2):325–344CrossRefGoogle Scholar
  34. Schmitt L, Tampe R (2002) Curr Opin Struct Biol 12(6):754–760CrossRefGoogle Scholar
  35. Seibert FS, Linsdell P, Loo TW, Hanrahan JW, Riordan JR et al (1996) J Biol Chem 271(44):27493–27499CrossRefGoogle Scholar
  36. Smith PC, Karpowich N, Millen L, Moody JE, Rosen J, et al (2002) Mol Cell 10(1):139–149CrossRefGoogle Scholar
  37. Sonnhammer EL, Eddy SR, Durbin R (1997) Proteins 28(3):405–420CrossRefGoogle Scholar
  38. Story RM, Weber IT, Steitz TA (1992) Nature 355(6358):318–325CrossRefGoogle Scholar
  39. Teem JL, Berger HA, Ostedgaard LS, Rich DP, Tsui LC et al (1993) Cell 73(2):335–346CrossRefGoogle Scholar
  40. Teem JL, Carson MR, Welsh MJ (1996) Recept Channels 4(1):63–72Google Scholar
  41. Thibodeau PH, Brautigam CA, Machius M, Thomas PJ (2005) Nat Struct Mol Biol 12(1):10–16CrossRefGoogle Scholar
  42. Vergani P, Lockless SW, Nairn AC, Gadsby DC (2005) Nature 433(7028):876–880CrossRefGoogle Scholar
  43. Walker JE, Saraste M, Runswick MJ, Gay NJ (1982) EMBO J 1(8):945–951Google Scholar
  44. Wigley WC, Vijayakumar S, Jones JD, Slaughter C, Thomas PJ (1998) Biochemistry 37(3):844–853CrossRefGoogle Scholar
  45. Zolnerciks JK, Wooding C, Linton KJ (2007) FASEB J 21(14):3937–3948CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Molecular Biophysics Graduate ProgramUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Department of PhysiologyUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.Department of PhysiologyUniversity of Texas Southwestern Medical CenterDallasUSA

Personalised recommendations