Gursky O, Aleshkov S
Department of Biophysics, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118-2526, USA.
Biochim Biophys Acta. 2000 Jan 3;1476(1):93-102. doi: 10.1016/s0167-4838(99)00228-9.
To probe the role of temperature in the conversion of soluble Alzheimer's beta-amyloid peptide (Abeta) to insoluble beta-sheet rich aggregates, we analyzed the solution conformation of Abeta(1-40) from 0 to 98 degrees C by far-UV circular dichroism (CD) and native gel electrophoresis. The CD spectra of 15-300 microg/ml Abeta(1-40) in aqueous solution (pH approximately 4.6) at 0 degrees C are concentration-independent and suggest a substantially unfolded and/or unusually folded conformation characteristic of Abeta monomer or dimer. Heating from 0 to 37 degrees C induces a rapid reversible coil to beta-strand transition that is independent of the peptide concentration and thus is not linked to oligomerization. Consequently, this transition may occur within the Abeta(1-40) monomer or dimer. Incubation at 37 degrees C leads to slow reversible concentration-dependent beta-sheet accumulation; heating to 85 degrees C induces further beta-sheet folding and oligomerization. Our results demonstrate the importance of temperature and thermal history for the conformation of Abeta.
为探究温度在可溶性阿尔茨海默病β-淀粉样肽（Aβ）转化为富含β-折叠的不溶性聚集体过程中的作用，我们通过远紫外圆二色光谱（CD）和天然凝胶电泳分析了0至98摄氏度下Aβ（1-40）的溶液构象。在0摄氏度时，15-300微克/毫升Aβ（1-40）在水溶液（pH约4.6）中的CD光谱与浓度无关，表明其具有Aβ单体或二聚体典型的基本未折叠和/或异常折叠的构象。从0摄氏度加热到37摄氏度会引发快速可逆的从无规卷曲到β-折叠链的转变，该转变与肽浓度无关，因此与寡聚化无关。所以，这种转变可能发生在Aβ（1-40）单体或二聚体内。在37摄氏度孵育会导致缓慢可逆的浓度依赖性β-折叠积累；加热到85摄氏度会诱导进一步的β-折叠和寡聚化。我们的结果证明了温度和热历史对Aβ构象的重要性。
