Ronga Luisa, Palladino Pasquale, Ragone Raffaele, Benedetti Ettore, Rossi Filomena
Dipartimento delle Scienze Biologiche and C.I.R.Pe.B., Università Federico II di Napoli, Naples, Italy.
J Pept Sci. 2009 Jan;15(1):30-5. doi: 10.1002/psc.1086.
On consideration that intrinsic structural weakness could affect the segment spanning the alpha2-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 180-195 C-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 alpha-type organization, consistently with the fact that the wild-type sequence is organized as an alpha-helix in the native protein. Moreover, the substitution of whatever single amino acid in the wild-type sequence reduced the gap between the alpha- and the beta-propensity, invariably enhancing the latter, but in any case this gap was larger than that evaluated for the full-length alpha2-helix-derived peptide. It appears that the low beta-conformation propensity of the 180-195 region depends on the simultaneous presence of all of the Ala-scanned residues, indirectly confirming that the N-terminal 173-179 segment could play a major role in determining the chameleon conformational behavior of the entire 173-195 region in the PrP.
鉴于内在结构弱点可能会影响朊蛋白中跨越α2螺旋残基173 - 195的片段，我们采用了一种理论基础源自蛋白质热力学的新方法，研究了一些源自180 - 195 C末端序列的肽的丙氨酸扫描合成类似物的构象稳定性。尽管无法对肽之间进行定量比较以根据单个氨基酸取代所产生的影响对它们进行排序，但总体趋势是，所有肽都始终表现出对α型结构的明显偏好，这与野生型序列在天然蛋白质中呈α螺旋结构这一事实一致。此外，野生型序列中任何单个氨基酸的取代都会缩小α倾向和β倾向之间的差距，总是增强后者，但在任何情况下，这个差距都大于对全长α2螺旋衍生肽评估的差距。看来180 - 195区域的低β构象倾向取决于所有丙氨酸扫描残基的同时存在，这间接证实了N末端173 - 179片段可能在决定朊蛋白中整个173 - 195区域的变色龙构象行为中起主要作用。
