Scrapie amyloid (prion) protein has the conformational characteristics of an aggregated molten globule folding intermediate.
Scrapie amyloid (prion) protein has the conformational characteristics of an aggregated molten globule folding intermediate.
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痒病淀粉样蛋白（朊病毒）具有聚集熔球折叠中间体的构象特征。
DOI：
10.1021/bi00193a027
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发表时间：
1994
期刊：
影响因子：
2.9
通讯作者：
C. Gibbs
中科院分区：
文献类型：
--
作者：
J. Safar;P. Roller;D. Gajdusek;C. Gibbs
瘙痒病淀粉样蛋白(PrP27-30)是感染性瘙痒病病原体的宿主来源成分；复制、繁殖和形成淀粉样蛋白的可能性是翻译后事件或构象异常的结果。在低浓度的盐酸胍(Gdn.HCl)中，PrP27-30在无极环境中解离为紧密的平衡中间体，具有很大一部分二级结构、部分变性的三级结构和色氨酸残基[Safar，J.，Roller，P.，Gajdusek，D.C.，&Gibbs，C.J.，Jr.(1993)J.Biol.化学。27,20276-20284]。在这里，我们描述了8-苯胺基-1-萘磺酸盐(ANS)荧光光谱和圆二色谱(CD)监测到的这种亚稳形式的特征，并提出了瘙痒淀粉样蛋白结合的机制。PrP27-30的Gdn.HCl诱导的平衡中间体与ANS有多个高亲和力疏水结合位点，其中一些靠近Trp残基。酸诱导的中间体(A-型)的酰胺CD谱在pH<；2.0处于平衡状态，与Gdn.HCl诱导的中间体相似，表明存在很大一部分α-螺旋或β-转角二级结构。相反，PrP27-30以全β片状构象结合成聚集体，具有较少的有序性和更多暴露的疏水侧链。Gdn.HCl诱导的中间体在高温下的非合作性展开是不可逆的，并与感染性的丧失有关。结果表明，PrP27-30通过致密的、亚稳态的疏水中间体与非天然、非变性的二级结构和接近未折叠形式的三级结构结合。
The scrapie amyloid (prion) protein (PrP27-30) is a host-derived component of the infectious scrapie agent; the potential to replicate, propagate, and form amyloid is a result of the posttranslational event or conformational abnormality. In low concentrations of guanidine hydrochloride (Gdn.HCl), PrP27-30 dissociates into a compact equilibrium intermediate with a substantial portion of secondary structure, partially denatured tertiary structure, and tryptophan residues in an apolar environment [Safar, J., Roller, P. P., Gajdusek, D. C., & Gibbs, C. J., Jr. (1993) J. Biol. Chem. 27, 20276-20284]. Here we describe the characteristics of this metastable form as monitored by 8-anilino-1-naphthalenesulfonate (ANS) fluorescence spectroscopy and circular dichroism (CD) spectroscopy, and we propose a mechanism for scrapie amyloid association. The Gdn.HCl-induced equilibrium intermediate of PrP27-30 had multiple high-affinity hydrophobic binding sites for ANS, some close to the Trp residues. The amide CD spectrum of an acid-induced intermediate (A-form), in equilibrium at pH < 2.0, was similar to the Gdn.HCl-induced intermediate and suggested the presence of a significant portion of an alpha-helical or beta-turn secondary structure. In contrast, the PrP27-30 associated into aggregates in an all beta-sheet conformation with less ordered and more exposed hydrophobic side chains. The noncooperative unfolding of the Gdn.HCl-induced intermediate at high temperature was irreversible and correlated with the loss of infectivity. The results demonstrate that PrP27-30 associates through a compact, metastable hydrophobic intermediate with an nonnative, nondenatured secondary structure and a tertiary structure close to the unfolded form.(ABSTRACT TRUNCATED AT 250 WORDS)
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DOI：
10.1016/s0021-9258(18)41985-0
发表时间：
1992-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
D. Borchelt;A. Taraboulos;S. Prusiner
通讯作者：
D. Borchelt;A. Taraboulos;S. Prusiner
影响因子：
2.9
作者：
N. Stahl;D. Borchelt;S. Prusiner
通讯作者：
N. Stahl;D. Borchelt;S. Prusiner
DOI：
10.1111/j.1432-1033.1988.tb14246.x
发表时间：
1988-09-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
TURK, E;TEPLOW, DB;PRUSINER, SB
通讯作者：
PRUSINER, SB
通过远紫外停流圆二色性和 8-苯胺基-1-萘磺酸盐结合测量大肠杆菌 trp 阻压剂早期折叠中间体的结构和稳定性。
影响因子：
2.9
作者：
Mann,CJ;Matthews,CR
通讯作者：
Matthews,CR
影响因子：
2.9
作者：
Matthews Cr;Crisanti Mm
通讯作者：
Matthews Cr;Crisanti Mm