MOLECULAR DYNAMICS STUDY OF CYTOCHROME C – LIPID COMPLEXES

  • V. Trusova Department of Nuclear and Medical Physics, V.N. Karazin Kharkiv National University4 Svobody Sq., Kharkiv, 61022, Ukraine http://orcid.org/0000-0002-7087-071X
  • G. Gorbenko Department of Nuclear and Medical Physics, V.N. Karazin Kharkiv National University4 Svobody Sq., Kharkiv, 61022, Ukraine http://orcid.org/0000-0002-0954-5053
  • U. Tarabara Department of Nuclear and Medical Physics, V.N. Karazin Kharkiv National University4 Svobody Sq., Kharkiv, 61022, Ukraine https://orcid.org/0000-0002-7677-0779
  • K. Vus Department of Nuclear and Medical Physics, V.N. Karazin Kharkiv National University4 Svobody Sq., Kharkiv, 61022, Ukraine http://orcid.org/0000-0003-4738-4016
  • O. Ryzhova Department of Nuclear and Medical Physics, V.N. Karazin Kharkiv National University4 Svobody Sq., Kharkiv, 61022, Ukraine http://orcid.org/0000-0001-9554-0090
Keywords: cytochrome c, protein-lipid interactions, amyloid, molecular dynamics

Abstract

The interactions between a mitochondrial hemoprotein cytochrome c (cyt c) and the model lipid membranes composed of zwitterionic lipid phosphatidylcholine (PC) and anionic lipids phosphatidylglycerol (PG), phosphatidylserine (PS) or cardiolipin (CL) were studied using the method of molecular dynamics. It was found that cyt c structure remains virtually unchanged in the protein complexes with PC/PG or PC/PS bilayers. In turn, protein binding to PC/CL bilayer is followed by the rise in cyt c radius of gyration and root-mean-square fluctuations. The magnitude of these changes was demonstrated to increase with the anionic lipid content. The revealed effect was interpreted in terms of the partial unfolding of polypeptide chain in the region Ala15-Leu32, widening of the heme crevice and enhancement of the conformational fluctuations in the region Pro76-Asp93 upon increasing the CL molar fraction from 5 to 25%. The results obtained seem to be of utmost importance in the context of amyloidogenic propensity of cyt c.

Downloads

Download data is not yet available.

References

1. Chiti F., Dobson C.M. Protein misfolding, amyloid formation, and human disease: a summary of progress over the last decade // Annu. Rev. Biochem. – 2017. – Vol. 86. – P. 27-68.

2. Kelly J.W. Towards an understanding of amyloidogenesis // Nat. Struct. Biol. – 2002. – Vol. 9. – P. 323-325.

3. Zbilut J.P., Colosimo A., Conti F., Colafranceschi M., Manetti C., Valerio M., Webber Jr. C. L., Giuliani A. Protein aggregation/folding: the role of deterministic singularities of sequence hydrophobicity as determined by nonlinear signal analysis of acylphosphatase and Aβ (1-40) // Biophys. J. – 2003. – Vol. 85. – P. 3544-3557.

4. Seelig J. Thermodynamics of lipid-peptide interactions // Biochim. Biophys. Acta. – 2004. – Vol. 1666. – P. 40-50.

5. Gsponer J., Vendruscolo M. Theoretical approaches to protein aggregation // Protein Pept. Lett. – 2006. – Vol. 13. – P. 287-293.

6. Dill K. A. Dominant forces in protein folding // Biochemistry. – 1990. – Vol. 29. – P. 7133-7155.

7. Bokvist M., Lindstrom F., Watts A., Grobner G. Two types of Alzheimer’s β-amyloid (1–40) peptide membrane interactions: aggregation preventing transmembrane anchoring versus accelerated surface fibril formation // J. Mol. Biol. – 2004. – Vol. 335. – P. 1039–1049.

8. Sharp J.S., Forrest J.A., Jones R.A.L. Surface denaturation and amyloid fibril formation of insulin at model lipid-water interfaces // Biochemistry – 2002. – Vol. 41. – P. 15810–15819.

9. Zhao H., Jutila A., Nurminen T., Wickstrom S.A., Keski-Oja J., Kinnunen P.K.J. Binding of endostatin to phosphatidylserine-containing membranes and formation of amyloid-like fibers // Biochemistry. – 2005. – Vol. 44. – P. 2857–2863.

10. Jo E., Darabie A.A., Han K., Tandon A., Frazer P.E., McLaurin J. α-synuclein – synaptosomal membrane interactions. Implications for fibrillogenesis // Eur. J. Biochem. – 2004. – Vol. 271. – P. 3180–3189.

11. Knight J.D., Miranker A.D. Phospholipid catalysis of diabetic amyloid assembly // J. Mol. Biol. – 2004. – Vol. 341. – P. 1175–1187.

12. Chirita C.N., Necula M., Kuret J. Anionic micelles and vesicles induce tau fibrillization in vitro // J. Biol. Chem. – 2003. – Vol. 278. – P. 25644–25650.

13. Zhao H., Tuominen E.K.J., Kinnunen P.K.J. Formation of amyloid fibers triggered by phosphatidylserine-containing membranes // Biochemistry. – 2003. – Vol. 43. – P. 10302–10307.

14. Uversky V.N., Fink A.L. Conformational constraints for amyloid fibrillation: the importance of being unfolded // Biochim. Biophys. Acta. – 2004. – Vol. 1698. – P. 131–153.

15. Gorbenko G. P., Kinnunen P. K. J. The role of lipid-protein interactions in amyloid-type protein fibril formation // Chem. Phys. Lipids. – 2006. – Vol. 141. – P. 72-82.

16. Wei G., Mousseau N., Derreumaux P. Computational simulations of early steps of protein aggregation // Prion. – 2007. – Vol. 1. – P. 3-8.

17. Avila C., Drechsel N., Alcantara R., Viila-Freixa J. Multiscale molecular dynamics of protein aggregation // Current Protein and Peptide Science. – 2011. – Vol. 12. – P. 221-234.

18. Beck D., Daggett V. Methods for molecular dynamics simulations of protein folding/unfolding in solution // Methods. – 2004. – Vol. 34. – P. 112-120.

19. Miao Y., Feixas F., Eun C., McCammon J.A. Accelerated molecular dynamics simulations of protein folding // J. Computat. Chem. – 2015. – Vol. 36. – P. 1536-1549.

20. Lemkul J.A., Bevan D.R. Assessing the stability of Alzheimer’s amyloid protofibrils using molecular dynamics // J. Phys. Chem. B. – 2010. – Vol. 114. – P. 1652-1660.

21. Diaz-Moreno I., Garcia-Heredia J.M., Diaz-Quitana A., De la Rosa M.A. Cytochrome c signalosome in mitochondria // Eur. Biophys. J. – 2011. – Vol. 40. – P. 1301–1315.

22. Goodsell D.S. The molecular perspective: cytochrome c and apoptosis // The Oncologist. – 2004. – Vol. 9. – P. 226–227.

23. Haldar S., Sil P., Thangamuniyandi M., Chattopadhyay K. Conversion of amyloid fibrils of cytochrome c to mature nanorods through a honeycomb morphology // Langmuir. – 2015. – Vol. 31. – P. 4213–4223.

24. Groot N.S., Ventura S. Amyloid fibril formation by bovine cytochrome c // Spectroscopy. – 2005. – Vol. 19. – P. 199–205.

25. Furkan M., Fazili N.A., Afsar M., Naeem A. Analysing cytochrome c aggregation and fibrillation upon interaction with acetonitrile: an in vitro study // J. Fluoresc. – 2016. – Vol. 26. – P. 1959–1966.

26. Hashimoto M., Takeda A., Hsu L.J., Takenouchi T., Masliah E. Role of cytochrome c as a stimulator of alpha-synuclein aggregation in Lewy body disease // J. Biol. Chem. – 1999. – Vol. 274. – P. 28849−28852.

27. Huang J., MacKerell A. CHARMM36 all-atom additive protein force field: validation based on comparison to NMR data // J. Comput. Chem. – 2013. – Vol. 34. – P. 2135–2145.

28. Lomize M., Pogozheva I., Joo H., Mosberg H., Lomize A. OPM database and PPM web server: resources for positioning of proteins in membranes // Nucl. Acids Res. – 2012. – Vol. 40. – P. 370–376.

29. Jo S., Lim J., Klauda J., Im W. CHARMM-GUI Membrane builder for mixed bilayers and its application to yeast membranes // Biophys. J. – 2009. – Vol. 97. – P. 50–58.

30. Darden T., York D., Pedersen L. Particle mesh Ewald: An N log(N) method for Ewald sums in large systems // J. Chem. Phys. – 1993. – Vol. 98. – P. 10089–10092.

31. Vehlow C., Stehr H., Winkelmann M., Duarte J., Petzold L., Dinse J., Lappe M. CMView: Interactive contact map visualization and analysis // Bioinformatics. – 2011. – Vol. 27. – P. 1573–1574.

32. Cortese J.D., Voglino A.L., Hackenbrock C.R. Multiple conformations of physiological membrane-bound cytochrome c // Biochemistry. – 1998. – Vol. 37. – P. 6402−6409.

33. Lewis R.N.A., McElhaney R.N. The physicochemical properties of cardiolipin bilayers and cardiolipin-containing lipid membranes // Biochim. Biophys. Acta. – 2009. – Vol. 1788. – P. 2069–2079.

34. Rytömaa M., Kinnunen P.K.J. Evidence for two distinct acidic phospholipid-binding sites in cytochrome c // J. Biol. Chem. – 1994. – Vol. 269. – P. 1770–1774.

35. Rytömaa M., Mustonen P., Kinnunen P.K.J. Reversible, nonionic, and pH-dependent association of cytochrome c with cardiolipin-phosphatidylcholine liposomes // J. Biol. Chem. – 1992. – Vol. 267. – P. 22243–22248.

36. Kalanhni E., Wallace C.J.A. Cytochrome c impaled: investigation of the extended lipid anchorage of a soluble protein to mitochondrial membrane models // Biochem. J. – 2007. – Vol. 407. – P. 179–187.

37. Sinibaldi F., Howes B.D., Droghetti E., Polticelli F., Piro M.C., Di Pierro D., Fiorucci L., Coletta M., Smulevich G., Santucci R. Role of lysines in cytochrome c–cardiolipin interaction // Biochemistry. – 2013. – Vol. 52. – P. 4578–4588.

38. Hanske J., Toffey J.R., Morenz A.M., Bonilla A.J., Schiavoni K.H., Pletneva E.V. Conformational properties of cardiolipin-bound cytochrome c // Proc. Natl. Acad. Sci. USA. – 2012. – Vol. 109. – P. 125–130.

39. Muenzner J., Pletneva E. Structural transformations of cytochrome c upon interaction with cardiolipin // Chem. Phys. Lipids. – 2014. – Vol. 179. – P. 57–63.

40. Pandiscia L.A., Schweitzer-Stenner R. Coexistence of native-like and non-native partially unfolded ferricytochrome c on the surface of cardiolipin-containing liposomes // J. Biol. Chem. B. – 2015. – Vol. 119. – P. 1334–1349.

41. Pinheiro T.J.T., Watts A. Lipid specificity in the interaction of cytochrome c with anionic phospholipid bilayers revealed by solid-state 31P NMR // Biochemistry. – 1994. – Vol. 33. – P. 2451–2458.

42. Pinheiro T.J.T., Cheng H., Seeholzer S.H., Roder H. Direct evidence for the cooperative unfolding of cytochrome c in lipid membranes from H-2H exchange kinetics // J. Mol. Biol. – 2003. – Vol. 303. – P. 617–626.

43. Belikova N.A., Vladimirov Y.A., Osipov A.N., Kapralov A.A., Tyurin V.A., Potapovich M.V., Basova L.V., Peterson J., Kurnikov I.V., Kagan V.E. Peroxidase activity and structural transitions of cytochrome c bound to cardiolipin-containing membranes // Biochemistry. – 2006. – Vol. 45. – P. 4998–5009.

44. Hong Y., Muenzner J., Grimm S.K., Pletneva E.V. Origin of the conformational heterogeneity of cardiolipin-bound cytochrome c // J. Amer. Chem. Soc. – 2012. – Vol. 134. – P. 18713–18723.

45. Brown L., Wuthrich K. NMR and ESR studies of the interactions of cytochrome c with mixed cardiolipin-phosphatidylcholine vesicles // Biochim. Biophys. Acta. – 1977. – Vol. 468. – P. 389–410.

46. De Kruijff B., Cullis P.R. Cytochrome c specifically induces non-bilayer structures in cardiolipin-containing model membranes // Biochim. Biophys. Acta. – 1980. – Vol. 602. – P. 477–490.

47. Bergstrom C.L., Beales P.A., Lv Y., Vanderlick T.K., Groves J.T. Cytochrome c causes pore formation in cardiolipin-containing membranes // Proc. Natl. Acad. Sci. USA. – 2013. – Vol. 110. – P. 6269–6274.

48. Spooner P.J.R., Watts A. Reversible unfolding of cytochrome c upon interaction with cardiolipin bilayers. 2. Evidence from phosphorus-31 NMR measurements // Biochemistry. – 1991. – Vol. 30. – P. 3880–3885.

49. Stepanov G., Gnedenko O., Mol’nar A., Ivanov A., Vladimirov Y., Osipov A. Evaluation of cytochrome c affinity to anionic phospholipids by means of surface plasmon resonance // FEBS Lett. – 2009. – Vol. 583. – P. 97–100.

50. Pinheiro T.J.T. The interaction of horse heart cytochrome c with phospholipid bilayers. Structural and dynamic effects // Biochimie. – 1994. – Vol. 76. – P. 489–500.

51. Hildebrandt P., Heimburg T., Marsh D. Quantitative conformational analysis of cytochrome c bound to phospholipid vesicles studied by resonance Raman spectroscopy // Eur. Biophys. J. – 1990. – Vol. 18. – P. 193–201.

52. Heimburg T., Hildebrandt P., Marsh D. Cytochrome c-lipid interactions studied by resonance Raman and 31P NMR spectroscopy. Correlation between the conformational changes of the protein and lipid bilayer // Biochemistry. – 1991. – Vol. 30. – P. 9084–9089.

53. Muenzner J., Toffey J., Hong Y., Pletneva E. Becoming a peroxidase: cardiolipin-induced unfolding of cytochrome c // J. Phys. Chem. B. – 2013. – Vol. 117. – P. 12878–12886.

54. Mandal A., Hoop C., DeLucia M., Kodali R., Kagan V., Ahn J., Wel P. Structural changes and proapoptotic peroxidase activity of cardiolipin-bound mitochondrial cytochrome c // Biophys. J. – 2015. – Vol. 109. – P. 1873–1884.

55. O’Brien E., Nucci N., Fuglestad B., Tommos C., Wand A.J. Defining the apoptotic trigger the interaction of cytochrome c and cardiolipin // J. Biol. Chem. – 2015. – Vol. 290. – P. 30879–30887.

56. Balakrishnan G., Hu Y., Spiro T. His26 protonation in cytochrome c triggers microsecond β-sheet formation and heme exposure: implications for apoptosis // J. Am. Chem. Soc. – 2012. – Vol. 134. – P. 19061–19069.

57. Bandi S., Bowler B. Probing the dynamics of a His73–heme alkaline transition in a destabilized variant of yeast iso-1-cytochrome c with conformationally gated electron transfer methods // Biochemistry. – 2011. – Vol. 50. – P. 10027–10040.
Published
2017-10-20
Cited
0 article
How to Cite
Trusova, V., Gorbenko, G., Tarabara, U., Vus, K., & Ryzhova, O. (2017). MOLECULAR DYNAMICS STUDY OF CYTOCHROME C – LIPID COMPLEXES. East European Journal of Physics, 4(3), 54-62. https://doi.org/10.26565/2312-4334-2017-3-08