Advertisement

Journal of Chemical Sciences

, Volume 127, Issue 12, pp 2159–2169 | Cite as

Modeling the structure of SARS 3a transmembrane protein using a minimum unfavorable contact approach

  • S RAMAKRISHNA
  • SILADITYA PADHI
  • U DEVA PRIYAKUMAREmail author
Article

Abstract

3a is an accessory protein from SARS coronavirus that is known to play a significant role in the proliferation of the virus by forming tetrameric ion channels. Although the monomeric units are known to consist of three transmembrane (TM) domains, there are no solved structures available for the complete monomer. The present study proposes a structural model for the transmembrane region of the monomer by employing our previously tested approach, which predicts potential orientations of TM α-helices by minimizing the unfavorable contact surfaces between the different TM domains. The best model structure comprising all three α-helices has been subjected to MD simulations to examine its quality. The TM bundle was found to form a compact and stable structure with significant intermolecular interactions. The structural features of the proposed model of 3a account for observations from previous experimental investigations on the activity of the protein. Further analysis indicates that residues from the TM2 and TM3 domains are likely to line the pore of the ion channel, which is in good agreement with a recent experimental study. In the absence of an experimental structure for the protein, the proposed structure can serve as a useful model for inferring structure-function relationships about the protein.

Graphical Abstract

The structure of the membrane protein 3a from SARS coronavirus is modeled using an approach that minimizes unfavorable contacts between transmembrane domains. A structure for a complete monomeric form of the protein thereby proposed is able to account for the behavior of the protein reported in previous experimental studies.

Keywords

Membrane protein modeling ion channel transmembrane helices viroporin molecular dynamics SARS 3a. 

Notes

Acknowledgments

This work was supported by the Department of Biotechnology, Ministry of Science and Technology, Government of India (Grant no. BT/PR12729/BID/07/297/ 2009). We thank Dr. Shahid Jameel for fruitful discussions and suggestions.

Supplementary material

12039_2015_982_MOESM1_ESM.doc (558 kb)
(DOC 558 KB)

References

  1. 1.
    Poutanen S M, Low D E, Henry B, Finkelstein S, Rose D, Green K, Tellier R, Draker R, Adachi D, Ayers M, Chan A K, Skowronski D M, Salit I, Simor A E, Slutsky A S, Doyle P W, Krajden M, Petric M, Brunham R C and McGeer A J 2003 N. Engl. J. Med. 348 1995CrossRefGoogle Scholar
  2. 2.
    Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt G M, Ahuja A, Yung M Y, Leung C B, To K F, Lui S F, Szeto C C, Chung S and Sung J J 2003 N. Engl. J. Med. 348 1986CrossRefGoogle Scholar
  3. 3.
    Tsang K W, Ho P L, Ooi G C, Yee W K, Wang T, Chan-Yeung M, Lam W K, Seto W H, Yam L Y, Cheung T M, Wong P C, Lam B, Ip M S, Chan J, Yuen K Y and Lai K N 2003 N. Engl. J. Med. 348 1977CrossRefGoogle Scholar
  4. 4.
    Drosten C, Günther S, Preiser W, van der Werf S, Brodt H R, Becker S, Rabenau H, Panning M, Kolesnikova L, Fouchier R A, Berger A, Burguière A M, Cinatl J, Eickmann M, Escriou N, Grywna K, Kramme S, Manuguerra J C, Müller S, Rickerts V, Stürmer M, Vieth S, Klenk H D, Osterhaus A D, Schmitz H and Doerr H W 2003 N. Engl. J. Med. 348 1967CrossRefGoogle Scholar
  5. 5.
    Ksiazek T G, Erdman D, Goldsmith C S, Zaki S R, Peret T, Emery S, Tong S, Urbani C, Comer J A, Lim W, Rollin P E, Dowell S F, Ling A E, Humphrey C D, Shieh W J, Guarner J, Paddock C D, Rota P, Fields B, DeRisi J, Yang J Y, Cox N, Hughes J M, LeDuc J W, Bellini W J and Anderson L J 2003 N. Engl. J. Med. 348 1953CrossRefGoogle Scholar
  6. 6.
    Marra M A, Jones S J, Astell C R, Holt R A, Brooks-Wilson A, Butterfield Y S, Khattra J, Asano J K, Barber S A, Chan S Y, Cloutier A, Coughlin S M, Freeman D, Girn N, Griffith O L, Leach S R, Mayo M, McDonald H, Montgomery S B, Pandoh P K, Petrescu A S, Robertson A G, Schein J E, Siddiqui A, Smailus D E, Stott J M, Yang G S, Plummer F, Andonov A, Artsob H, Bastien N, Bernard K, Booth T F, Bowness D, Czub M, Drebot M, Fernando L, Flick R, Garbutt M, Gray M, Grolla A, Jones S, Feldmann H, Meyers A, Kabani A, Li Y, Normand S, Stroher U, Tipples G A, Tyler S, Vogrig R, Ward D, Watson B, Brunham R C, Krajden M, Petric M, Skowronski D M, Upton C and Roper R L 2003 Science 300 1399CrossRefGoogle Scholar
  7. 7.
    Rota P A, Oberste M S, Monroe S S, Nix W A, Campagnoli R, Icenogle J P, Peñaranda S, Bankamp B, Maher K, Chen M H, Tong S, Tamin A, Lowe L, Frace M, DeRisi J L, Chen Q, Wang D, Erdman D D, Peret T C, Burns C, Ksiazek T G, Rollin P E, Sanchez A, Liffick S, Holloway B, Limor J, McCaustland K, Olsen-Rasmussen M, Fouchier R, Günther S, Osterhaus A D, Drosten C, Pallansch M A, Anderson L J and Bellini W J 2003 Science 300 1394CrossRefGoogle Scholar
  8. 8.
    Lai M and Holmes K 2001 In Fields Virology D M Knipe and P M Howley (eds.) (Philadelphia: Lippincott-Willams and Wilkins) p. 1163Google Scholar
  9. 9.
    Holmes K V and Enjuanes L 2003 Science 300 1377CrossRefGoogle Scholar
  10. 10.
    Snijder E J, Bredenbeek P J, Dobbe J C, Thiel V, Ziebuhr J, Poon L L, Guan Y, Rozanov M, Spaan W J and Gorbalenya A E 2003 J. Mol. Biol. 331 991CrossRefGoogle Scholar
  11. 11.
    Lu W, Zheng B J, Xu K, Schwarz W, Du L, Wong C K, Chen J, Duan S, Deubel V and Sun B 2006 Proc. Natl. Acad. Sci. USA 103 12540CrossRefGoogle Scholar
  12. 12.
    Berman H M, Westbrook J, Feng Z, Gilliland G, Bhat T N, Weissig H, Shindyalov I N and Bourne P E 2000 Nucleic Acids Res. 8 235CrossRefGoogle Scholar
  13. 13.
    Lear J D, Stouffer A L, Gratkowski H, Nanda V and Degrado W F 2004 Biophys. J. 87 3421CrossRefGoogle Scholar
  14. 14.
    Senes A, Engel D E and DeGrado W F 2004 Curr. Opin. Struct. Biol. 14 465CrossRefGoogle Scholar
  15. 15.
    Nath D 2005 Nature 438 577CrossRefGoogle Scholar
  16. 16.
    Popot J L and Engelman D M 1990 Biochemistry 29 4031CrossRefGoogle Scholar
  17. 17.
    Popot J L and Engelman D M 2000 Annu. Rev. Biochem. 69 881CrossRefGoogle Scholar
  18. 18.
    Feller S E, Gawrisch K and Woolf T B 2003 J. Am. Chem. Soc. 125 4434CrossRefGoogle Scholar
  19. 19.
    Lindahl E and Sansom M S P 2008 Curr. Opin. Struct. Biol. 18 425CrossRefGoogle Scholar
  20. 20.
    White S H and Wimley W C 1999 Annu. Rev. Biophys. Biomol. Struct. 28 319CrossRefGoogle Scholar
  21. 21.
    Johansson A C and Lindahl E 2006 Biophys. J. 91 4450CrossRefGoogle Scholar
  22. 22.
    MacCallum J L, Bennett W F D and Tieleman D P 2007 J. Gen. Physiol. 129 371CrossRefGoogle Scholar
  23. 23.
    MacCallum J L, Bennet W F D and Tieleman D P 2008 Biophys. J. 94 3393CrossRefGoogle Scholar
  24. 24.
    Biggin P C and Sansom M S 1999 Biophys. Chem. 76 161CrossRefGoogle Scholar
  25. 25.
    Forrest L R and Sansom M S P 2000 Curr. Opin. Struct. Biol. 10 174CrossRefGoogle Scholar
  26. 26.
    Domene C, Bond P J and Sansom M S P 2003 Adv. Protein Chem. 66 159CrossRefGoogle Scholar
  27. 27.
    Nymeyer H, Woolf T B and Garcia A E 2005 Proteins 59 783CrossRefGoogle Scholar
  28. 28.
    Woolf T B, Zuckerman D M and Lu N D 2004 J. Mol. Graph. 22 359CrossRefGoogle Scholar
  29. 29.
    Efremov R G, Nolde D E, Konshina A G, Syrtcev N P and Arseniev A S. 2004 Curr. Med. Chem. 11 2421CrossRefGoogle Scholar
  30. 30.
    Krüger J and Fischer W B 2009 J. Chem. Theory Comput. 5 2503CrossRefGoogle Scholar
  31. 31.
    Hao-Jen H and Fischer W B 2011 J. Mol. Model. 18 501Google Scholar
  32. 32.
    Goldman D E 1943 J. Gen. Physiol. 27 37CrossRefGoogle Scholar
  33. 33.
    Chien T H, Chiang Y, Chen C P, Henklein P, Hanel K, Hwang I S, Willbold D and Fischer W 2013 Biopolymers 99 628CrossRefGoogle Scholar
  34. 34.
    Hodgkin A L and Katz B 1949 J. Physiol. 108 37CrossRefGoogle Scholar
  35. 35.
    Jäckle J 2007 J. Theor. Biol. 249 445CrossRefGoogle Scholar
  36. 36.
    Padhi S, Ramakrishna S and Priyakumar U D 2015 J. Comput. Chem. 36 539CrossRefGoogle Scholar
  37. 37.
    The Sybyl Software, version 7.2 2006 (St Louis, MO, USA: Tripos Inc.)Google Scholar
  38. 38.
    Im W, Lee M S and Brooks I. C L 2003 J. Comput. Chem. 24 1691CrossRefGoogle Scholar
  39. 39.
    Im W M, Feig M and Brooks I. C L 2003 Biophys. J. 85 2900CrossRefGoogle Scholar
  40. 40.
    Brooks B R, Brooks I. C L, MacKerell A D J., Nilsson L, Petrella R J, Roux B, Won Y, Archontis G, Bartels C, Boresch S, Caflisch A, Caves L, Cui Q, Dinner A R, Feig M, Fischer S, Gao J, Hodoscek M, Im W, Kuczera K, Lazaridis T, Ma J, Ovchinnikov V, Paci E, Pastor R W, Post C B, Pu J Z, Schaefer M, Tidor B, Venable R M, Woodcock H L, Wu X, Yang W, York D M and Karplus M 2009 J. Comput. Chem. 30 1545CrossRefGoogle Scholar
  41. 41.
    MacKerell A D J., Bashford D, Bellott M, Dunbrack R L, Evanseck J D, Field M J, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau F T, Mattos C, Michnick S, Ngo T, Nguyen D T, Prodhom B, Reiher W E, Roux B, Schlenkrich M, Smith J C, Stote R, Straub J, Watanabe M, Wiórkiewicz-Kuczera J, Yin D and Karplus M 1998 J. Phys. Chem. B 102 3586CrossRefGoogle Scholar
  42. 42.
    MacKerell A D J., Feig M and Brooks I. C. 2004 J. Comput. Chem. 25 1400CrossRefGoogle Scholar
  43. 43.
    Phillips J C, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel R D, Kale L and Schulten K 2005 J. Comput. Chem. 26 1781CrossRefGoogle Scholar
  44. 44.
    Humphrey W, Dalke A and Schulten K 1996 J. Molec. Graphics 14 33CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2015

Authors and Affiliations

  • S RAMAKRISHNA
    • 1
  • SILADITYA PADHI
    • 1
  • U DEVA PRIYAKUMAR
    • 1
    Email author
  1. 1.Center for Computational Natural Sciences and BioinformaticsInternational Institute of Information TechnologyHyderabadIndia

Personalised recommendations