2wut Citations

Structural and functional characterization of human peripheral nervous system myelin protein P2.

Abstract

The myelin sheath is a tightly packed multilayered membrane structure insulating selected axons in the central and the peripheral nervous systems. Myelin is a biochemically unique membrane, containing a specific set of proteins. In this study, we expressed and purified recombinant human myelin P2 protein and determined its crystal structure to a resolution of 1.85 A. A fatty acid molecule, modeled as palmitate based on the electron density, was bound inside the barrel-shaped protein. Solution studies using synchrotron radiation indicate that the crystal structure is similar to the structure of the protein in solution. Docking experiments using the high-resolution crystal structure identified cholesterol, one of the most abundant lipids in myelin, as a possible ligand for P2, a hypothesis that was proven by fluorescence spectroscopy. In addition, electrostatic potential surface calculations supported a structural role for P2 inside the myelin membrane. The potential membrane-binding properties of P2 and a peptide derived from its N terminus were studied. Our results provide an enhanced view into the structure and function of the P2 protein from human myelin, which is able to bind both monomeric lipids inside its cavity and membrane surfaces.

Articles - 2wut mentioned but not cited (6)

  1. Structural and functional characterization of human peripheral nervous system myelin protein P2. Majava V, Polverini E, Mazzini A, Nanekar R, Knoll W, Peters J, Natali F, Baumgärtel P, Kursula I, Kursula P. PLoS One 5 e10300 (2010)
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  3. Atomic resolution view into the structure-function relationships of the human myelin peripheral membrane protein P2. Ruskamo S, Yadav RP, Sharma S, Lehtimäki M, Laulumaa S, Aggarwal S, Simons M, Bürck J, Ulrich AS, Juffer AH, Kursula I, Kursula P. Acta Crystallogr D Biol Crystallogr 70 165-176 (2014)
  4. Structural Basis for the Selective Inhibition of Cdc2-Like Kinases by CX-4945. Lee JY, Yun JS, Kim WK, Chun HS, Jin H, Cho S, Chang JH. Biomed Res Int 2019 6125068 (2019)
  5. Production and crystallization of a panel of structure-based mutants of the human myelin peripheral membrane protein P2. Lehtimäki M, Laulumaa S, Ruskamo S, Kursula P. Acta Crystallogr Sect F Struct Biol Cryst Commun 68 1359-1362 (2012)
  6. Cryo-EM, X-ray diffraction, and atomistic simulations reveal determinants for the formation of a supramolecular myelin-like proteolipid lattice. Ruskamo S, Krokengen OC, Kowal J, Nieminen T, Lehtimäki M, Raasakka A, Dandey VP, Vattulainen I, Stahlberg H, Kursula P. J Biol Chem 295 8692-8705 (2020)


Reviews citing this publication (5)

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Articles citing this publication (24)

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  3. A role of peripheral myelin protein 2 in lipid homeostasis of myelinating Schwann cells. Zenker J, Stettner M, Ruskamo S, Domènech-Estévez E, Baloui H, Médard JJ, Verheijen MH, Brouwers JF, Kursula P, Kieseier BC, Chrast R. Glia 62 1502-1512 (2014)
  4. A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy. Hong YB, Joo J, Hyun YS, Kwak G, Choi YR, Yeo HK, Jwa DH, Kim EJ, Mo WM, Nam SH, Kim SM, Yoo JH, Koo H, Park HT, Chung KW, Choi BO. PLoS Genet 12 e1005829 (2016)
  5. Charge isomers of myelin basic protein: structure and interactions with membranes, nucleotide analogues, and calmodulin. Wang C, Neugebauer U, Bürck J, Myllykoski M, Baumgärtel P, Popp J, Kursula P. PLoS One 6 e19915 (2011)
  6. Enhanced axonal neuregulin-1 type-III signaling ameliorates neurophysiology and hypomyelination in a Charcot-Marie-Tooth type 1B mouse model. Scapin C, Ferri C, Pettinato E, Zambroni D, Bianchi F, Del Carro U, Belin S, Caruso D, Mitro N, Pellegatta M, Taveggia C, Schwab MH, Nave KA, Feltri ML, Wrabetz L, D'Antonio M. Hum Mol Genet 28 992-1006 (2019)
  7. Structure of the dimeric autoinhibited conformation of DAPK2, a pro-apoptotic protein kinase. Patel AK, Yadav RP, Majava V, Kursula I, Kursula P. J Mol Biol 409 369-383 (2011)
  8. Molecular mechanisms of Charcot-Marie-Tooth neuropathy linked to mutations in human myelin protein P2. Ruskamo S, Nieminen T, Kristiansen CK, Vatne GH, Baumann A, Hallin EI, Raasakka A, Joensuu P, Bergmann U, Vattulainen I, Kursula P. Sci Rep 7 6510 (2017)
  9. Neuregulin 1 type III improves peripheral nerve myelination in a mouse model of congenital hypomyelinating neuropathy. Belin S, Ornaghi F, Shackleford G, Wang J, Scapin C, Lopez-Anido C, Silvestri N, Robertson N, Williamson C, Ishii A, Taveggia C, Svaren J, Bansal R, Schwab MH, Nave K, Fratta P, D'Antonio M, Poitelon Y, Feltri ML, Wrabetz L. Hum Mol Genet 28 1260-1273 (2019)
  10. Structural and dynamical properties of reconstituted myelin sheaths in the presence of myelin proteins MBP and P2 studied by neutron scattering. Knoll W, Peters J, Kursula P, Gerelli Y, Ollivier J, Demé B, Telling M, Kemner E, Natali F. Soft Matter 10 519-529 (2014)
  11. How Does Protein Zero Assemble Compact Myelin? Raasakka A, Kursula P. Cells 9 E1832 (2020)
  12. Structure and dynamics of a human myelin protein P2 portal region mutant indicate opening of the β barrel in fatty acid binding proteins. Laulumaa S, Nieminen T, Raasakka A, Krokengen OC, Safaryan A, Hallin EI, Brysbaert G, Lensink MF, Ruskamo S, Vattulainen I, Kursula P. BMC Struct Biol 18 8 (2018)
  13. The Role of Peripheral Myelin Protein 2 in Remyelination. Stettner M, Zenker J, Klingler F, Szepanowski F, Hartung HP, Mausberg AK, Kleinschnitz C, Chrast R, Kieseier BC. Cell Mol Neurobiol 38 487-496 (2018)
  14. The myelin protein PMP2 is regulated by SOX10 and drives melanoma cell invasion. Graf SA, Heppt MV, Wessely A, Krebs S, Kammerbauer C, Hornig E, Strieder A, Blum H, Bosserhoff AK, Berking C. Pigment Cell Melanoma Res 32 424-434 (2019)
  15. Conformations of peptides derived from myelin-specific proteins in membrane-mimetic conditions probed by synchrotron radiation CD spectroscopy. Myllykoski M, Baumgärtel P, Kursula P. Amino Acids 42 1467-1474 (2012)
  16. Dynamics of the Peripheral Membrane Protein P2 from Human Myelin Measured by Neutron Scattering--A Comparison between Wild-Type Protein and a Hinge Mutant. Laulumaa S, Nieminen T, Lehtimäki M, Aggarwal S, Simons M, Koza MM, Vattulainen I, Kursula P, Natali F. PLoS One 10 e0128954 (2015)
  17. High-resolution structural model of porcine P2 myelin membrane protein with associated fatty acid ligand: fact or artifact? Sedzik J, Jastrzebski JP. J Neurosci Res 89 909-920 (2011)
  18. Identification of a pathogenic PMP2 variant in a multi-generational family with CMT type 1: Clinical gene panels versus genome-wide approaches to molecular diagnosis. Punetha J, Mackay-Loder L, Harel T, Coban-Akdemir Z, Jhangiani SN, Gibbs RA, Lee I, Terespolsky D, Lupski JR, Posey JE. Mol Genet Metab 125 302-304 (2018)
  19. Production, crystallization and neutron diffraction of fully deuterated human myelin peripheral membrane protein P2. Laulumaa S, Blakeley MP, Raasakka A, Moulin M, Härtlein M, Kursula P. Acta Crystallogr F Struct Biol Commun 71 1391-1395 (2015)
  20. Peripheral myelin protein 2 - a novel cluster of mutations causing Charcot-Marie-Tooth neuropathy. Palaima P, Chamova T, Jander S, Mitev V, Van Broeckhoven C, Tournev I, Peeters K, Jordanova A. Orphanet J Rare Dis 14 197 (2019)
  21. Sub-Atomic Resolution Crystal Structures Reveal Conserved Geometric Outliers at Functional Sites. Laulumaa S, Kursula P. Molecules 24 E3044 (2019)
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  23. Influence of myelin proteins on the structure and dynamics of a model membrane with emphasis on the low temperature regime. Knoll W, Peters J, Kursula P, Gerelli Y, Natali F. J Chem Phys 141 205101 (2014)
  24. Effect of hindlimb unloading on myelinated fibers in the mouse lumbar spinal cord. Islamov RR, Lannik NI, Shaimardanova GF, Rezvyakov PN, Tyapkina OV, Rizvanov AA, Chelyshev YA, Kozlovskaya IB, Nikolskii EE. Dokl Biol Sci 452 266-268 (2013)