Structural analysis of the complex between calmodulin and full-length myelin basic protein, an intrinsically disordered molecule

Viivi Majava, Chaozhan Wang, Matti Myllykoski, Salla M. Kangas, Sung Ung Kang, Nobuhiro Hayashi, Peter Baumgärtel, Anthony M. Heape, Gert Lubec, Petri Kursula

Research output: Contribution to journalArticle

Abstract

Myelin basic protein (MBP) is present between the cytoplasmic leaflets of the compact myelin membrane in both the peripheral and central nervous systems, and characterized to be intrinsically disordered in solution. One of the best-characterized protein ligands for MBP is calmodulin (CaM), a highly acidic calcium sensor. We pulled down MBP from human brain white matter as the major calcium-dependent CaM-binding protein. We then used full-length brain MBP, and a peptide from rodent MBP, to structurally characterize the MBP-CaM complex in solution by small-angle X-ray scattering, NMR spectroscopy, synchrotron radiation circular dichroism spectroscopy, and size exclusion chromatography. We determined 3D structures for the full-length protein-protein complex at different stoichiometries and detect ligand-induced folding of MBP. We also obtained thermodynamic data for the two CaM-binding sites of MBP, indicating that CaM does not collapse upon binding to MBP, and show that CaM and MBP colocalize in myelin sheaths. In addition, we analyzed the post-translational modifications of rat brain MBP, identifying a novel MBP modification, glucosylation. Our results provide a detailed picture of the MBP-CaM interaction, including a 3D model of the complex between full-length proteins.

Original languageEnglish (US)
Pages (from-to)59-71
Number of pages13
JournalAmino Acids
Volume39
Issue number1
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

Keywords

  • 3-dimensional structure
  • Calmodulin
  • Myelin
  • Myelin basic protein
  • Protein complex
  • Proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Majava, V., Wang, C., Myllykoski, M., Kangas, S. M., Kang, S. U., Hayashi, N., Baumgärtel, P., Heape, A. M., Lubec, G., & Kursula, P. (2010). Structural analysis of the complex between calmodulin and full-length myelin basic protein, an intrinsically disordered molecule. Amino Acids, 39(1), 59-71. https://doi.org/10.1007/s00726-009-0364-2