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

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...

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Bibliographic Details
Published in:Amino acids 2010-06, Vol.39 (1), p.59-71
Main Authors: Majava, Viivi, Wang, Chaozhan, Myllykoski, Matti, Kangas, Salla M, Kang, Sung Ung, Hayashi, Nobuhiro, Baumgärtel, Peter, Heape, Anthony M, Lubec, Gert, Kursula, Petri
Format: Article
Language:English
Subjects:
3-dimensional structure
Analytical Chemistry
Animals
Biochemical Engineering
Biochemistry
Biomedical and Life Sciences
Brain
calmodulin
Calmodulin - chemistry
Cattle
Cells, Cultured
Humans
Life Sciences
Ligands
Mice
Models, Molecular
Myelin basic protein
Myelin Basic Protein - chemistry
myelin sheath
Neurobiology
Original Article
Protein Binding
Protein complex
Protein Conformation
Protein Folding
Proteins
Proteomics
Spectrum analysis
Swine
Thermodynamics
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Summary: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.
ISSN:0939-4451
1438-2199
DOI:10.1007/s00726-009-0364-2