The conversion of prion helix 1 from an alpha-helical into an extended conformation is generally assumed to be an essential step in the conversion of the cellular isoform PrPC of the prion protein to the pathogenic isoform PrPSc. Peptides encompassing helix 1 and flanking sequences were analyzed by nuclear magnetic resonance and circular dichroism. Our results indicate a remarkably high instrinsic helix propensity of the helix 1 region. In particular, these peptides retain significant helicity under a wide range of conditions, such as high salt, pH variation, and presence of organic co-solvents. As evidenced by a data base search, the pattern of charged residues present in helix 1 generally favors helical structures over alternative conformations. Because of its high stability against environmental changes, helix 1 is unlikely to be involved in the initial steps of the pathogenic conformational change. Our results implicate that interconversion of helix 1 is rather representing a barrier than a nucleus for the PrPC-->PrPSc conversion.
Toward the Molecular Basis of Inherited Prion Diseases: NMR Structure of the Human Prion Protein with V210I Mutation.
Toward the Molecular Basis of Inherited Prion Diseases: NMR Structure of the Human Prion Protein with V210I Mutation.
Toward the Molecular Basis of Inherited Prion Diseases: NMR Structure of the Human Prion Protein with V210I Mutation.
J Mol Biol. 2011 Aug 4;
Authors: Biljan I, Ilc G, Giachin G, Raspadori A, Zhukov I, Plavec J, Legname G
The development of transmissible spongiform encephalopathies (TSEs) is associated with the conversion of the cellular prion protein (PrP(C)) into a misfolded, pathogenic isoform (PrP(Sc)). Spontaneous generation...
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[NMR paper] Solid-state NMR studies of the secondary structure of a mutant prion protein fragment
Solid-state NMR studies of the secondary structure of a mutant prion protein fragment of 55 residues that induces neurodegeneration.
Related Articles Solid-state NMR studies of the secondary structure of a mutant prion protein fragment of 55 residues that induces neurodegeneration.
Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11686-90
Authors: Laws DD, Bitter HM, Liu K, Ball HL, Kaneko K, Wille H, Cohen FE, Prusiner SB, Pines A, Wemmer DE
The secondary structure of a 55-residue fragment of the mouse prion protein, MoPrP(89-143), was studied in...
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11-19-2010 08:44 PM
[NMR paper] NMR studies of the sporulation protein SpoIIAA: implications for the regulation of th
NMR studies of the sporulation protein SpoIIAA: implications for the regulation of the transcription factor sigmaF in Bacillus subtilis.
Related Articles NMR studies of the sporulation protein SpoIIAA: implications for the regulation of the transcription factor sigmaF in Bacillus subtilis.
J Biomol NMR. 2001 Apr;19(4):293-304
Authors: Kovacs H, Comfort D, Lord M, Yudkin M, Campbell ID, Nilges M
SpoIIAA participates in a four-component mechanism for phosphorylation-dependent transcription control at the outset of sporulation. We report the...
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[NMR paper] NMR relaxation studies of the role of conformational entropy in protein stability and
NMR relaxation studies of the role of conformational entropy in protein stability and ligand binding.
Related Articles NMR relaxation studies of the role of conformational entropy in protein stability and ligand binding.
Acc Chem Res. 2001 May;34(5):379-88
Authors: Stone MJ
Recent advances in the measurement and analysis of protein NMR relaxation data have made it possible to characterize the dynamical properties of many backbone and side chain groups. With certain caveats, changes in flexibility that occur upon ligand binding, mutation, or...
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[NMR paper] NMR structure of the sterol carrier protein-2: implications for the biological role.
NMR structure of the sterol carrier protein-2: implications for the biological role.
Related Articles NMR structure of the sterol carrier protein-2: implications for the biological role.
J Mol Biol. 2000 Jan 21;295(3):595-603
Authors: García FL, Szyperski T, Dyer JH, Choinowski T, Seedorf U, Hauser H, Wüthrich K
The determination of the NMR structure of the sterol carrier protein-2 (SCP2), analysis of backbone (15)N spin relaxation parameters and NMR studies of nitroxide spin-labeled substrate binding are presented as a new basis for...
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[NMR paper] Prion protein fragments spanning helix 1 and both strands of beta sheet (residues 125
Prion protein fragments spanning helix 1 and both strands of beta sheet (residues 125-170) show evidence for predominantly helical propensity by CD and NMR.
Related Articles Prion protein fragments spanning helix 1 and both strands of beta sheet (residues 125-170) show evidence for predominantly helical propensity by CD and NMR.
Fold Des. 1998;3(5):313-20
Authors: Sharman GJ, Kenward N, Williams HE, Landon M, Mayer RJ, Searle MS
BACKGROUND: Transmissible spongiform encephalopathies are a group of neurodegenerative disorders of man and animals...
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[NMR paper] Prion protein NMR structure and species barrier for prion diseases.
Prion protein NMR structure and species barrier for prion diseases.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-pnas_full_free.gif http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.pubmedcentral.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.gif Related Articles Prion protein NMR structure and species barrier for prion diseases.
Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7281-5
Authors: Billeter M, Riek R, Wider G, Hornemann S, Glockshuber R, Wüthrich K
The structural...
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[NMR paper] Solid-state NMR studies of the prion protein H1 fragment.
Solid-state NMR studies of the prion protein H1 fragment.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.interscience.wiley.com-aboutus-images-wiley_interscience_pubmed_logo_FREE_120x27.gif http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.pubmedcentral.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.gif Related Articles Solid-state NMR studies of the prion protein H1 fragment.
Protein Sci. 1996 Aug;5(8):1655-61
Authors: Heller J, Kolbert AC, Larsen R, Ernst M, Bekker T, Baldwin M, Prusiner SB, Pines A, Wemmer DE
Conformational...
CD and NMR studies of prion protein (PrP) helix 1. Novel implications for its role in
Linear Mode
