A thermodynamic approach to the conformational preferences of the 180–195 segment derived from the human prion protein α2‐helix
作者:
Luisa Ronga,
Pasquale Palladino,
Raffaele Ragone,
Ettore Benedetti,
Filomena Rossi,
期刊:
Journal of Peptide Science
(WILEY Available online 2009)
卷期:
Volume 15,
issue 1
页码: 30-35
ISSN:1075-2617
年代: 2009
DOI:10.1002/psc.1086
出版商: John Wiley&Sons, Ltd.
关键词: prion protein;α2‐helix;β‐sheet;amyloid;transmissible spongiform encephalopathies;CD titration;prion toxicity;structure‐inducing agents
数据来源: WILEY
摘要:
AbstractOn consideration that intrinsic structural weakness could affect the segment spanning the α2‐helical residues 173–195 of the PrP, we have investigated the conformational stabilities of some synthetic Ala‐scanned analogs of the peptide derived from the 180–195C‐terminal sequence, using a novel approach whose theoretical basis originates from protein thermodynamics. Even though a quantitative comparison among peptides could not be assessed to rank them according to the effect caused by single amino acid substitution, as a general trend, all peptides invariably showed an appreciable preference for an α‐type organization, consistently with the fact that the wild‐type sequence is organized as an α‐helix in the native protein. Moreover, the substitution of whatever single amino acid in the wild‐type sequence reduced the gap between the α‐ and the β‐propensity, invariably enhancing the latter, but in any case this gap was larger than that evaluated for the full‐length α2‐helix‐derived peptide. It appears that the low β‐conformation propensity of the 180–195 region depends on the simultaneous presence of all of the Ala‐scanned residues, indirectly confirming that theN‐terminal 173–179 segment could play a major role in determining the chameleon conformational behavior of the entire 173–195 region in the PrP. Copyright © 2008 Eu
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