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. 1999 Oct;77(4):1753–1768. doi: 10.1016/S0006-3495(99)77022-0

Steered molecular dynamics simulation of the Rieske subunit motion in the cytochrome bc(1) complex.

S Izrailev 1, A R Crofts 1, E A Berry 1, K Schulten 1
PMCID: PMC1300462  PMID: 10512801

Abstract

Crystallographic structures of the mitochondrial ubiquinol/cytochrome c oxidoreductase (cytochrome bc(1) complex) suggest that the mechanism of quinol oxidation by the bc(1) complex involves a substantial movement of the soluble head of the Rieske iron-sulfur protein (ISP) between reaction domains in cytochrome b and cytochrome c(1) subunits. In this paper we report the results of steered molecular dynamics simulations inducing, through an applied torque within 1 ns, a 56 degrees rotation of the soluble domain of ISP. For this purpose, a solvated structure of the bc(1) complex in a phospholipid bilayer (a total of 206,720 atoms) was constructed. A subset of 91,061 atoms was actually simulated with 45,131 moving atoms. Point charge distributions for the force field parametrization of heme groups and the Fe(2)S(2) cluster of the Rieske protein included in the simulated complex were determined. The simulations showed that rotation of the soluble domain of ISP is actually feasible. Several metastable conformations of the ISP during its rotation were identified and the interactions stabilizing the initial, final, and intermediate positions of the soluble head of the ISP domain were characterized. A pathway for proton conduction from the Q(o) site to the solvent via a water channel has been identified.

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Selected References

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  1. Abrahams J. P., Leslie A. G., Lutter R., Walker J. E. Structure at 2.8 A resolution of F1-ATPase from bovine heart mitochondria. Nature. 1994 Aug 25;370(6491):621–628. doi: 10.1038/370621a0. [DOI] [PubMed] [Google Scholar]
  2. Balsera M., Stepaniants S., Izrailev S., Oono Y., Schulten K. Reconstructing potential energy functions from simulated force-induced unbinding processes. Biophys J. 1997 Sep;73(3):1281–1287. doi: 10.1016/S0006-3495(97)78161-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  4. Bishop T. C., Kosztin D., Schulten K. How hormone receptor-DNA binding affects nucleosomal DNA: the role of symmetry. Biophys J. 1997 May;72(5):2056–2067. doi: 10.1016/S0006-3495(97)78849-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brandt U. Proton-translocation by membrane-bound NADH:ubiquinone-oxidoreductase (complex I) through redox-gated ligand conduction. Biochim Biophys Acta. 1997 Jan 16;1318(1-2):79–91. doi: 10.1016/s0005-2728(96)00141-7. [DOI] [PubMed] [Google Scholar]
  6. Brandt U. The chemistry and mechanics of ubihydroquinone oxidation at center P (Qo) of the cytochrome bc1 complex. Biochim Biophys Acta. 1998 Jun 10;1365(1-2):261–268. doi: 10.1016/s0005-2728(98)00078-4. [DOI] [PubMed] [Google Scholar]
  7. Brandt U., Trumpower B. The protonmotive Q cycle in mitochondria and bacteria. Crit Rev Biochem Mol Biol. 1994;29(3):165–197. doi: 10.3109/10409239409086800. [DOI] [PubMed] [Google Scholar]
  8. Connolly M. L. Solvent-accessible surfaces of proteins and nucleic acids. Science. 1983 Aug 19;221(4612):709–713. doi: 10.1126/science.6879170. [DOI] [PubMed] [Google Scholar]
  9. Crofts A. R., Berry E. A. Structure and function of the cytochrome bc1 complex of mitochondria and photosynthetic bacteria. Curr Opin Struct Biol. 1998 Aug;8(4):501–509. doi: 10.1016/s0959-440x(98)80129-2. [DOI] [PubMed] [Google Scholar]
  10. Dalke A., Schulten K. Using Tcl for molecular visualization and analysis. Pac Symp Biocomput. 1997:85–96. [PubMed] [Google Scholar]
  11. Elston T., Wang H., Oster G. Energy transduction in ATP synthase. Nature. 1998 Jan 29;391(6666):510–513. doi: 10.1038/35185. [DOI] [PubMed] [Google Scholar]
  12. Elston T., Wang H., Oster G. Energy transduction in ATP synthase. Nature. 1998 Jan 29;391(6666):510–513. doi: 10.1038/35185. [DOI] [PubMed] [Google Scholar]
  13. Gennis R. B., Barquera B., Hacker B., Van Doren S. R., Arnaud S., Crofts A. R., Davidson E., Gray K. A., Daldal F. The bc1 complexes of Rhodobacter sphaeroides and Rhodobacter capsulatus. J Bioenerg Biomembr. 1993 Jun;25(3):195–209. doi: 10.1007/BF00762582. [DOI] [PubMed] [Google Scholar]
  14. Grubmüller H., Heymann B., Tavan P. Ligand binding: molecular mechanics calculation of the streptavidin-biotin rupture force. Science. 1996 Feb 16;271(5251):997–999. doi: 10.1126/science.271.5251.997. [DOI] [PubMed] [Google Scholar]
  15. Humphrey W., Dalke A., Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996 Feb;14(1):33-8, 27-8. doi: 10.1016/0263-7855(96)00018-5. [DOI] [PubMed] [Google Scholar]
  16. Isralewitz B., Izrailev S., Schulten K. Binding pathway of retinal to bacterio-opsin: a prediction by molecular dynamics simulations. Biophys J. 1997 Dec;73(6):2972–2979. doi: 10.1016/S0006-3495(97)78326-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Iwata S., Lee J. W., Okada K., Lee J. K., Iwata M., Rasmussen B., Link T. A., Ramaswamy S., Jap B. K. Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex. Science. 1998 Jul 3;281(5373):64–71. doi: 10.1126/science.281.5373.64. [DOI] [PubMed] [Google Scholar]
  18. Iwata S., Saynovits M., Link T. A., Michel H. Structure of a water soluble fragment of the 'Rieske' iron-sulfur protein of the bovine heart mitochondrial cytochrome bc1 complex determined by MAD phasing at 1.5 A resolution. Structure. 1996 May 15;4(5):567–579. doi: 10.1016/s0969-2126(96)00062-7. [DOI] [PubMed] [Google Scholar]
  19. Izrailev S., Stepaniants S., Balsera M., Oono Y., Schulten K. Molecular dynamics study of unbinding of the avidin-biotin complex. Biophys J. 1997 Apr;72(4):1568–1581. doi: 10.1016/S0006-3495(97)78804-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kim H., Xia D., Yu C. A., Xia J. Z., Kachurin A. M., Zhang L., Yu L., Deisenhofer J. Inhibitor binding changes domain mobility in the iron-sulfur protein of the mitochondrial bc1 complex from bovine heart. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8026–8033. doi: 10.1073/pnas.95.14.8026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kosztin D., Bishop T. C., Schulten K. Binding of the estrogen receptor to DNA. The role of waters. Biophys J. 1997 Aug;73(2):557–570. doi: 10.1016/S0006-3495(97)78093-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kosztin D., Izrailev S., Schulten K. Unbinding of retinoic acid from its receptor studied by steered molecular dynamics. Biophys J. 1999 Jan;76(1 Pt 1):188–197. doi: 10.1016/S0006-3495(99)77188-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lancaster C. R., Michel H. The coupling of light-induced electron transfer and proton uptake as derived from crystal structures of reaction centres from Rhodopseudomonas viridis modified at the binding site of the secondary quinone, QB. Structure. 1997 Oct 15;5(10):1339–1359. doi: 10.1016/s0969-2126(97)00285-2. [DOI] [PubMed] [Google Scholar]
  24. Link T. A. The role of the 'Rieske' iron sulfur protein in the hydroquinone oxidation (Q(P)) site of the cytochrome bc1 complex. The 'proton-gated affinity change' mechanism. FEBS Lett. 1997 Jul 28;412(2):257–264. doi: 10.1016/s0014-5793(97)00772-2. [DOI] [PubMed] [Google Scholar]
  25. Lu H., Isralewitz B., Krammer A., Vogel V., Schulten K. Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation. Biophys J. 1998 Aug;75(2):662–671. doi: 10.1016/S0006-3495(98)77556-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mitchell P. Possible molecular mechanisms of the protonmotive function of cytochrome systems. J Theor Biol. 1976 Oct 21;62(2):327–367. doi: 10.1016/0022-5193(76)90124-7. [DOI] [PubMed] [Google Scholar]
  27. Noji H., Yasuda R., Yoshida M., Kinosita K., Jr Direct observation of the rotation of F1-ATPase. Nature. 1997 Mar 20;386(6622):299–302. doi: 10.1038/386299a0. [DOI] [PubMed] [Google Scholar]
  28. Wriggers W., Schulten K. Investigating a back door mechanism of actin phosphate release by steered molecular dynamics. Proteins. 1999 May 1;35(2):262–273. [PubMed] [Google Scholar]
  29. Wriggers W., Schulten K. Protein domain movements: detection of rigid domains and visualization of hinges in comparisons of atomic coordinates. Proteins. 1997 Sep;29(1):1–14. [PubMed] [Google Scholar]
  30. Xia D., Yu C. A., Kim H., Xia J. Z., Kachurin A. M., Zhang L., Yu L., Deisenhofer J. Crystal structure of the cytochrome bc1 complex from bovine heart mitochondria. Science. 1997 Jul 4;277(5322):60–66. doi: 10.1126/science.277.5322.60. [DOI] [PubMed] [Google Scholar]
  31. Zhang L., Hermans J. Hydrophilicity of cavities in proteins. Proteins. 1996 Apr;24(4):433–438. doi: 10.1002/(SICI)1097-0134(199604)24:4<433::AID-PROT3>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
  32. Zhang Z., Huang L., Shulmeister V. M., Chi Y. I., Kim K. K., Hung L. W., Crofts A. R., Berry E. A., Kim S. H. Electron transfer by domain movement in cytochrome bc1. Nature. 1998 Apr 16;392(6677):677–684. doi: 10.1038/33612. [DOI] [PubMed] [Google Scholar]

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