Journal of Bioenergetics and Biomembranes

, Volume 29, Issue 6, pp 525–531 | Cite as

On the Structure and Gating Mechanism of the Mitochondrial Channel, VDAC

  • Carmen A. Mannella


There is considerable evidence that the voltage-gated mitochondrial channel VDAC forms a β-barrel pore. Inferences about the number and tilt of β-strands can be drawn from comparisons with bacterial β-barrel pores whose structures have been determined by x-ray crystallography. A structural model for VDAC is proposed (based on sequence analysis and electron crystallography) in which the open state is like that of bacterial porins with several important differences. Because VDAC does not occur as close-packed trimers, there are probably fewer interpore contacts than in the bacterial porins. VDAC also appears to lack a large, fixed intraluminal segment and may not have as extensive a region of uniformly 35°-tilted β-strands as do the bacterial porins. These structural differences would be expected to render VDAC's β-barrel less stable than its bacterial counterparts, making major conformational changes like those associated with gating more energetically feasible. A possible gating mechanism is suggested in which movement of the N-terminal α-helix out of the lumen wall triggers larger-scale structural changes.

Porin ion channel mitochondria VDAC electron microscopy sequence analysis β-barrel 


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  1. Benz, R. (1994). Biochim. Biophys. Acta 1197, 167–196.Google Scholar
  2. Benz, R., Darveaux, R. P., and Hancock, R. E. W. (1984). Eur. J. Biochem. 140, 319–324.Google Scholar
  3. Benz, R., Schmid, A., and Hancock, R. E. W. (1985). J. Bacteriol. 162, 722–727.Google Scholar
  4. Benz, R., Kottke, M., and Brdiczka, D. (1990). Biochim. Biophys. Acta 1022, 311–318.Google Scholar
  5. Blachly-Dyson, E., Peng, S. Z., Colombini, M., and Forte, M. (1990). Science 247, 1233–1236.Google Scholar
  6. Colombini, M., Yeung, C. L., Tung, J., and König, T. (1987). Biochim. Biophys. Acta 905, 279–286.Google Scholar
  7. Colombini, M., Blachly-Dyson, E., and Forte, M. (1996). In Ion Channels, Vol. 4, Plenum Press, New York, pp. 169–202.Google Scholar
  8. Cowan, S. W., Schirmer, T., Rummel, G., Steiert, M., Ghosh, R., Pauptit, R. A., Jansonius, J. N., and Rosenbusch, J. P. (1992). Nature 358, 727–733.Google Scholar
  9. De Pinto, V., Prezioso, G., Thinnes, F., Link, T. A., and Palmieri, F. (1991). Biochemistry 30, 10191–10200.Google Scholar
  10. Forte, M., Guy, H. R., and Mannella, C. A. (1987). J. Bioenerg. Biomembr. 19, 341–350.Google Scholar
  11. Guo, X. W., and Mannella, C. A. (1993). Biophys. J. 64, 545–549.Google Scholar
  12. Guo, X. W., Smith, P. R., Cognon, B., D'Arcangelis, D., Dolginova, E., and Mannella, C. A. (1995). J. Struct. Biol. 114, 41–59.Google Scholar
  13. Holden, M. J., and Colombini, M. (1993). Biochim. Biophys. Acta 1144, 396–402.Google Scholar
  14. Kleene, R., Pfanner, N., Pfaller, R., Link, T., Sebald, W., Neupert, W., and Tropschug, M. (1987). EMBO J. 6, 2627–2633.Google Scholar
  15. Koppel, D. A., Kinnally, K. W., and Mannella, C. A. (1997). Biophys. J. 72, A38.Google Scholar
  16. Lawrence, C. E., Altschul, S. F., Boguski, M. S., Liu, J. S., Neuwald, A. F., and Wootton, J. C. (1993). Science 262, 208–214.Google Scholar
  17. Liu, M. Y., and Colombini, M. (1992). Biochim. Biophys. Acta 1098, 255–260.Google Scholar
  18. Mannella, C. A. (1984). Science 224, 165–166.Google Scholar
  19. Mannella, C. A. (1990). Experientia 46, 137–145.Google Scholar
  20. Mannella, C. A. (1997). In Proc. Microscopy and Microanalyas 1997, Springer Verlag, New York, pp. 1065–1066.Google Scholar
  21. Mannella, C. A., and Guo, X. W. (1992). Trans. ACA 28, 176–182.Google Scholar
  22. Mannella, C. A., Guo, X. W., and Cognon, B. (1989). FEBS Lett. 253, 231–234.Google Scholar
  23. Mannella, C. A. Forte, M., and Colombini, M. (1992). J. Bioenerg. Biomembr. 24, 7–19.Google Scholar
  24. Mannella, C. A., Neuwald, A. F., and Lawrence, C. E. (1996). J. Bioenerg. Biomembr. 28, 161–167.Google Scholar
  25. Neuwald, A. F., Liu, J. S., and Lawrence, C. E. (1995). Protein Sci. 4, 1618–1632.Google Scholar
  26. Peng, S., Blachly-Dyson, E., Forte, M., and Colombini, M. (1992). Biophys. J. 62, 123–135.Google Scholar
  27. Popp, B., Court, D. A., Benz, R., Neupert, W., and Lill, R. (1996). J. Biol. Chem. 271, 13593–13599.Google Scholar
  28. Rauch, G., and Moran, O. (1994). Biochem. Biophys. Res. Commun. 200, 908–915.Google Scholar
  29. Roos, N., Benz, R. and Brdiczka, D. (1982). Biochim. Biophys. Acta 686, 204–214.Google Scholar
  30. Rostovtseva, T., and Colombini, M. (1996). J. Biol. Chem. 271, 28006–28008.Google Scholar
  31. Shao, L., Kinnally, K. W., and Mannella, C. A. (1996). Biophys. J. 71, 778–786.Google Scholar
  32. Song, J., and Colombini, M. (1996). J. Bioenerg. Biomembr. 28, 153–161.Google Scholar
  33. Song, L., Hobaugh, M. R., Shustak, C., Cheley, S., Bayley, H., and Gouaux, J. E. (1996). Science 274, 1859–1866.Google Scholar
  34. Stanley, S., and Mannella, C. A. (1997). Biophys. J. 72, A347.Google Scholar
  35. Stanley, S., Dias, J. A., D'Arcangelis, D., and Mannella, C. A. (1995). J. Biol. Chem. 270, 16694–16700.Google Scholar
  36. Thomas, L., Blachly-Dyson, E., Colombini, M., and Forte, M. (1993). Proc. Natl. Acad. Sci. USA 90, 5446–5449.Google Scholar
  37. Weiss, M. S., and Schulz, G. E. (1992). J. Mol. Biol. 227, 493–509.Google Scholar
  38. Weiss, M. S., Kieusch, A., Schiltz, E., Nestel, U., Welte. W., Weckesser, J., and Schulz, G. E. (1991). FEBS Lett. 280, 379–382.Google Scholar
  39. Zizi, M., Forte, M., Blachly-Dyson, E., and Colombini, M. (1994). J. Biol. Chem. 269, 1614–1616.Google Scholar
  40. Zizi, M., Thomas, L., Blachly-Dyson, E., Forte, M., and Colombini, M. (1995). J. Membr. Biol. 144, 121–129.Google Scholar

Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • Carmen A. Mannella
    • 1
    • 2
  1. 1.Division of Molecular MedicineWadsworth Center, New York State Department of HealthAlbany
  2. 2.Department of Biomedical Sciences, School of Public HealthUniversity at Albany (SUNY)Albany

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