Abstracts

Knowledge of the tertiary structure of myelin basic protein (MBP) is essential to understanding the organi sation of the myelin membrane and the mechanisms of development of autoimmunity in mult iple sclerosis. We have initiated high-resolution electron micro scopical (EM) analyses of MBP to determine its structure. When imaged as individual particles, MBP demonstrates a “C” shap e in proj ect ion, of approximately 1.5 nm in thickness and 8 nm in length . Two-dimensional crystallisation experiments on MBP using mono layers of DHAA (dehydroabietylamine) or lipid mixtures (phosphatidylcholine, phosphatid ylserine, dioleoyl phosphatidylethanolamine, galactocerebroside) yielded lamellar or occasion ally cry stalline structures with a repeating pattern of packed protein molecules with a unit cell size of approximately 2 nm by 7 nm, suggesting that the MBP extends itself upon interac tion with the monolayer. Molecular modelling of MBP based on a proposal by Stoner (J. Neurochem. 43 , 433–447,1984), using coo rdin ates of the B sheet backbone of bacteriochlorophyll A protein and energy min imis ation, yielded a compact structure of size and appearance consistent with both our EM data and with biochemical data on accessibility of specific sires (e.g., Ser7, Thr98) to modification . The bend of the C shape appears due to a natura l curvature in the B sheet. These results are fully congruous with MBP having a regular secondary structure and domains that are potentially flexible with respect to one another. This work was supported by the Multiple Sclerosis Society of Canada.

Authors and Affiliations

1. Department of Molecular Biology & Genetics, University of Guelph, Guelph, Ontario, N1G 2W1, Canada

   D. R. Beniac, R. A. Ridsdale, M. D. Luckevich, T. A. Tompkins & G. Harauz

2. Laboratoire R&D, Lallemand Inc., 6100, Royalmount, Montreal, Quebec, H4P 2R2, Canada

   T. A. Tompkins

3. Department of Biochemistry, Uppsala University, BMC Box 576, Uppsala, 751-23, Sweden

   J. Sedzik, S. Hjertén, E. Brekkan & P. Lundahl

4. Samuel Lunenfeld Research Institute at Mt. Sinai Hospital, Toronto, Ontario, Canada

   Michael B. Tropak & John C. Roder

5. AutoImmune, Inc., 128 Spring St., Lexington, Massachusetts, 02173, USA

   F. Giordano, B. Chang, A. M. La Ronde, A. Al-Sabbagh & M. Kretschmer

6. Department of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK

   A. Asipu & G. E. Blair

7. Department of Biochemistry Research, Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada

   B. Mak & M. A. Moscarello

8. Department of Anatomy & Cell Biology and the Multiple Sclerosis and Neuroscience Research Center, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5, Canada

   R. Doucette, K. Gratto, V. Verge, A. Nazarali & B. H. J. Juurlink

9. Laboratory of Molecular Biology, College of Pharmarmacy & Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5, Canada

   R. Doucette

10. Health Protection Branch, Sir Frederick Banting Research Centre, Ottawa, ON, Canada

    J. Yeung

11. Unité 368 de l’Institut National de la Santé et de la recherche Medicale, Ecole Normale Supérieure, 46, rue d’Ulm, Paris, 75230, France

    P. Murphy, P. Topilko, S. Schneider-Maunoury, T. Seitanidou & P. Charnay

12. Unité 134 de l’Institut National de la Santé et de la recherche Medicale, Hôpital de la Salpêtriere, Paris, 75651, France

    A. Baron-Van Evercooren

13. Department of Anatomy and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, England

    M. J. Lee, A. Brennan, A. Tabernero, Z. Dong, A. Blanchard, G. Zoidl, K. R. Jessen & R. Mirsky

14. Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile

    E. Couve, F. Cabello, J. Krsulovic & M. Roncagliolo

15. Department of Physiology, University of Manitoba, Winnipeg, Manitoba, R3E 0W3, Canada

    J. Li, E. L. Hertzberg & J. I. Nagy

16. Department of Cell Biology, ETH Hönggerberg, Zürich, CH-8093, Switzerland

    Dirk H.-H. Neuberg & Ueli Suter

17. Department of Neurobiology, ETH Hönggerberg, Zürich, CH-8093, Switzerland

    Patrizia Anzini, Melitta Schachner & Rudolf Martini

18. Institut für Genetik, Abteilung Molekulargenetik, Universität Bonn, Bonn, D-53117, Germany

    Eric Nelles & Klaus Willecke

19. University of Konstanz, Konstanz, D-78434, Germany

    R. Ankerhold & C. A. O. Stuermer

20. National Institutes of Health, NINDS-LDN, Bethesda, MD, USA

    Karen J. Chandross & L. D. Hudson

21. Department of Neurology, Albert Einstein College Medicine, Bronx, New York, USA

    W. T. Norton & R. I. Cohen

22. Department of Neurology and Immunology, Mayo Clinic Foundation, Rochester, Minnesota, 55905, USA

    K. Asakura, S. F. Hunter & M. Rodriguez

23. Departments of Pharmacology and Microbiology, and Program in Neurological Sciences, University of Connecticut Medical School, Farmington, CT, 6030-3205, USA

    Rashmi Bansal, Susan Winkler & S. E. Pfeiffer

24. Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, H3A 2B4, Canada

    Y. S. Oh. & V. W. Yong

25. Department of Surgery (Neurosurgery) and the Multiple Sclerosis and Neuroscience Research Center, University of Saskatchewan, Saskatoon, S7N 5E5, Saskatchewan, Canada

    R. W. Griebel

26. Department of Oral Biology and the Multiple Sclerosis and Neuroscience Research Center, University of Saskatchewan, Saskatoon, S7N 5E5, Saskatchewan, Canada

    R. M. Devon

27. Department of Pharmacology, McGill University, Montreal, H3G 1Y6, Quebec, Canada

    A. Khorchid & G. Almazan

28. Department of Pharmacology and Therapeutics, McGill University, Montreal, H3G 1Y6, Quebec, Canada

    G. Almazan & H.-N. Liu

29. Department of Anatomy, West Virginia University Medical School, P.O.Box 9128, Morgantown, 26506-9128, West Virginia, USA

    G. W. Konat, Gu Jin & R. C. Wiggins

30. Department of Anatomy and Cell Biology & the Saskatchewan Stroke Research Centre, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5, Canada

    B. H. J. Juurlink, S. K. Thorburne & S. E. Jelinski

31. Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada

    B. L. Bartnik & R. M. Devon

32. Departments of Pharmacology and Anatomy & Cell Biology & the Saskatchewan Stroke Research Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    B. H. J. Juurlink, H. Marrif & L. Hertz

33. Departments of Pediatrics & the Saskatchewan Stroke Research Centre, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5, Canada

    J. Y. Yager

34. Departments of Pathology and Biochemistry, University of Manitoba, Winnipeg, MB, R3E 0W3, Canada

    M. R. Del Bigio & J. N. Kanfer

35. AutoImmune, Inc., Lexington, MA, 02173, USA

    A. Al-Sabbagh, H. L. Weiner & P. A. Nelson

36. Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA

    A. Al-Sabbagh, H. L. Weiner & P. A. Nelson

37. Depts. Zoology, UBC, 6270 University Boulevard, Vancouver, BC, V6T 1Z4, Canada

    J. K. Dyer, J. Bourque & J. D. Steeves

38. Depts. Anatomy, UBC, 6270 University Boulevard, Vancouver, BC, V6T 1Z4, Canada

    J. D. Steeves

39. Depts. Surgery, UBC, 6270 University Boulevard, Vancouver, BC, V6T 1Z4, Canada

    J. D. Steeves

40. Samuel Lunenfeld Research Institute, Toronto, MSG 1X5, Ontario, Canada

    John C. Roder & Monika Labes

41. Allelix Biopharmaceuticals Inc., Mississauga, L4V IV7, Ontario, Canada

    Arthur Roach

42. Cameco MS Neuroscience Research Center and Dept. of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, S7N 5E5, Canada

    Parker L. Andersen, David J. Schreyer, L. A. Karchewski & V. M. K. Verge

43. Dept. of Zoology, University of Columbia, Vancouver, BC, Canada

    J. L. Vanderluit & W. Tetzlaff

44. McGill University, Montreal, Canada

    A. Peterson

45. Molecular Neurobiology Lab, Heinrich-Heine-University, Dusseldorf, Germany

    C. O. Hanemann & H. W. Mueller

46. Institute of Neurology Nijmegen, Netherlands

    A. Gabreëls-Festen

47. College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Sk., S7N 5C9, Canada

    M. Foldvari & M. R. Jaafari

Editors and Affiliations

1. University of Saskatchewan, Saskatoon, Saskatchewan, Canada

   Bernhard H. J. Juurlink , Richard M. Devon , J. Ronald Doucette , Adil J. Nazarali , David J. Schreyer  & Valerie M. K. Verge , , , ,  & 

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