Related ArticlesSolid-State NMR Spectroscopy of Membrane-Associated Myelin Basic Protein-Conformation and Dynamics of an Immunodominant Epitope.
Biophys J. 2010 Aug 9;99(4):1247-1255
Authors: Ahmed MA, Bamm VV, Harauz G, Ladizhansky V
Myelin basic protein (MBP) maintains the tight multilamellar compaction of the myelin sheath in the central nervous system through peripheral binding of adjacent lipid bilayers of oligodendrocytes. Myelin instability in multiple sclerosis (MS) is associated with the loss of positive charge in MBP as a result of posttranslational enzymatic deimination. A highly-conserved central membrane-binding fragment (murine N81-PVVHFFKNIVTPRTPPP-S99, identical to human N83-S101) represents a primary immunodominant epitope in MS. Previous low-resolution electron paramagnetic resonance measurements on the V83-T92 fragment, with Cys-mutations and spin-labeling that scanned the epitope, were consistent with it being a membrane-associated amphipathic alpha-helix. Pseudodeimination at several sites throughout the protein, all distal to the central segment, disrupted the alpha-helix at its amino-terminus and exposed it to proteases, representing a potential mechanism in the autoimmune pathogenesis of MS. Here, we have used magic-angle spinning solid-state NMR spectroscopy to characterize more precisely the molecular conformation and dynamics of this central immunodominant epitope of MBP in a lipid milieu, without Cys-substitution. Our solid-state NMR measurements have revealed that the alpha-helix present within the immunodominant epitope is shorter than originally modeled, and is independent of the pseudodeimination, highlighting the importance of the local hydrophobic effects in helix formation and stability. The main effect of pseudodeimination is to cause the cytoplasmic exposure of the fragment, potentially making it more accessible to proteolysis. These results are the first, to our knowledge, to provide atomic-level detail of a membrane-anchoring segment of MBP, and direct evidence of decreased MBP-membrane interaction after posttranslational modification.
PMID: 20713009 [PubMed - as supplied by publisher]
Solid-State NMR on a Large Multidomain Integral Membrane Protein: The Outer Membrane Protein Assembly Factor BamA.
Solid-State NMR on a Large Multidomain Integral Membrane Protein: The Outer Membrane Protein Assembly Factor BamA.
Solid-State NMR on a Large Multidomain Integral Membrane Protein: The Outer Membrane Protein Assembly Factor BamA.
J Am Chem Soc. 2011 Mar 1;
Authors: Renault M, Bos MP, Tommassen J, Baldus M
Multidomain proteins constitute a large part of prokaryotic and eukaryotic proteomes and play fundamental roles in various physiological processes. However, their structural characterization is challenging because of their large size and...
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Solid-State NMR on a Large Multidomain Integral Membrane Protein: The Outer Membrane Protein Assembly Factor BamA
Solid-State NMR on a Large Multidomain Integral Membrane Protein: The Outer Membrane Protein Assembly Factor BamA
Marie Renault, Martine P. Bos, Jan Tommassen and Marc Baldus
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja109469c/aop/images/medium/ja-2010-09469c_0004.gif
Journal of the American Chemical Society
DOI: 10.1021/ja109469c
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/jacsat/~4/9XN1qiW-S-I
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03-02-2011 02:01 AM
[NMR paper] Determination of membrane protein structure and dynamics by magic-angle-spinning solid-state NMR spectroscopy.
Determination of membrane protein structure and dynamics by magic-angle-spinning solid-state NMR spectroscopy.
Related Articles Determination of membrane protein structure and dynamics by magic-angle-spinning solid-state NMR spectroscopy.
J Am Chem Soc. 2005 Sep 21;127(37):12965-74
Authors: Andronesi OC, Becker S, Seidel K, Heise H, Young HS, Baldus M
It is shown that molecular structure and dynamics of a uniformly labeled membrane protein can be studied under magic-angle-spinning conditions. For this purpose, dipolar recoupling experiments...
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12-01-2010 06:56 PM
[NMR paper] How to prepare membrane proteins for solid-state NMR: A case study on the alpha-helical integral membrane protein diacylglycerol kinase from E. coli.
How to prepare membrane proteins for solid-state NMR: A case study on the alpha-helical integral membrane protein diacylglycerol kinase from E. coli.
Related Articles How to prepare membrane proteins for solid-state NMR: A case study on the alpha-helical integral membrane protein diacylglycerol kinase from E. coli.
Chembiochem. 2005 Sep;6(9):1693-700
Authors: Lorch M, Faham S, Kaiser C, Weber I, Mason AJ, Bowie JU, Glaubitz C
Several studies have demonstrated that it is viable to use microcrystalline preparations of water-soluble proteins as...
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12-01-2010 06:56 PM
[NMR paper] Investigation of the interaction of myelin basic protein with phospholipid bilayers u
Investigation of the interaction of myelin basic protein with phospholipid bilayers using solid-state NMR spectroscopy.
Related Articles Investigation of the interaction of myelin basic protein with phospholipid bilayers using solid-state NMR spectroscopy.
Chem Phys Lipids. 2004 Nov;132(1):47-54
Authors: Pointer-Keenan CD, Lee DK, Hallok K, Tan A, Zand R, Ramamoorthy A
Interaction of bovine myelin basic protein and its constituent charge isomers (C1-C3) with phospholipid bilayers was studied using solid-state NMR experiments on model...
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11-24-2010 10:03 PM
[NMR paper] NMR and molecular dynamics studies of an autoimmune myelin basic protein peptide and
NMR and molecular dynamics studies of an autoimmune myelin basic protein peptide and its antagonist: structural implications for the MHC II (I-Au)-peptide complex from docking calculations.
Related Articles NMR and molecular dynamics studies of an autoimmune myelin basic protein peptide and its antagonist: structural implications for the MHC II (I-Au)-peptide complex from docking calculations.
Eur J Biochem. 2004 Aug;271(16):3399-413
Authors: Tzakos AG, Fuchs P, van Nuland NA, Troganis A, Tselios T, Deraos S, Matsoukas J, Gerothanassis IP, Bonvin AM
...
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[NMR paper] Proton NMR study of peptides from myelin basic protein: evidence for Lys74-His77 inte
Proton NMR study of peptides from myelin basic protein: evidence for Lys74-His77 interaction revealed from histidine line broadening.
Related Articles Proton NMR study of peptides from myelin basic protein: evidence for Lys74-His77 interaction revealed from histidine line broadening.
Biochim Biophys Acta. 1996 Mar 7;1293(1):23-30
Authors: Koshy KM, Hashim GA, Boggs JM
Residues 69-84 of guinea pig myelin basic protein contain the encephalitogenic determinant for the Lewis rat. Insertion of histidine and glycine at positions 77 and 78 in bovine...
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08-22-2010 02:27 PM
[NMR paper] Interaction of myelin basic protein with single bilayers on a solid support: an NMR,
Interaction of myelin basic protein with single bilayers on a solid support: an NMR, DSC and polarized infrared ATR study.
Related Articles Interaction of myelin basic protein with single bilayers on a solid support: an NMR, DSC and polarized infrared ATR study.
Biochim Biophys Acta. 1993 Sep 19;1151(2):127-36
Authors: Reinl HM, Bayerl TM
The interaction of myelin basic protein (MBP) with single bilayers on a solid support (planar and spherical support) is studied by deuterium nuclear magnetic resonance (2H-NMR), differential scanning...