Selective molecular recognition in amyloid growth and transmission and cross-species barriers.
Selective molecular recognition in amyloid growth and transmission and cross-species barriers.
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DOI：
10.1016/j.jmb.2011.11.023
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发表时间：
2012-08-10
影响因子：
5.6
通讯作者：
Nussinov R
中科院分区：
文献类型：
--
作者：
Ma B;Nussinov R
相互构象选择和群体转移，其次是轻微的诱导拟合优化是生物分子识别的关键机制;单体和小寡聚体在原纤维生长中与淀粉样蛋白种子结合是分子识别事件。在这里，我们描述了淀粉样蛋白聚集，优选的物种，跨物种的障碍和分子识别的广泛框架内的传输。淀粉样蛋白种类的交叉播种受相容（互补）状态的构象选择支配。如果两个物种的优势构象相似，它们可以相互交叉播种;另一方面，如果它们足够不同，它们将生长成不同的原纤维，反映物种障碍。这种情况最近已经在具有四个重复的tau蛋白中观察到。虽然由重复序列1、3和4组成的构建体可以作为整个4-重复序列tau片段的种子，但反过来并不成立。另一方面，具有特征性U形转弯形状的tau蛋白重复序列可以交叉接种阿尔茨海默氏Aβ，并且类似地胰岛淀粉样多肽（IAPP）。在这个框架内，我们认为，所谓的“中心法则”的淀粉样蛋白的形成，聚集发生通过非特异性骨架氢键相互作用，这是常见的所有肽和蛋白质，是一个简单的反映的异质性，多态性的自由能景观的淀粉样蛋白物种。在这里，我们回顾了现有的数据，并提出了一些解决这一关键问题的建议。特别是，我们认为，最近的理论和实验观察支持的关键作用，选择性分子识别淀粉样变性和确定跨物种的障碍和传输。
Mutual conformational selection and population shift followed by minor induced fit optimization is the key mechanism in biomolecular recognition; and monomers and small oligomers binding to amyloid seeds in fibril growth is a molecular recognition event. Here, we describe amyloid aggregation, preferred species, cross-species barriers and transmission within the broad framework of molecular recognition. Cross seeding of amyloid species is governed by conformational selection of compatible (complementary) states. If the dominant conformations of two species are similar, they can cross-seed each other; on the other hand, if they are sufficiently different, they will grow into different fibrils, reflecting species barriers. Such a scenario has recently been observed for the tau protein which has four repeats. While a construct consisting of repeats 1, 3 and 4 can serve as a seed for the entire 4-repeat tau segment, the inverse does not hold. On the other hand, the tau protein repeats with the characteristic U-turn shape can cross-seed Alzheimer’s Aβ, and similarly the Islet Amyloid Polypeptide (IAPP). Within this framework, we suggest that the so-called ‘central dogma’ of amyloid formation, where aggregation takes place through non-specific backbone hydrogen bonding interactions which are common to all peptides and proteins, is a simple reflection of the heterogeneous, polymorphic free energy landscape of amyloid species. Here, we review available data and make some propositions addressing this key problem. In particular, we argue that recent theoretical and experimental observations support the key role of selective molecular recognition in amyloidosis and in determining cross-species barriers and transmission.
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影响因子：
2.9
作者：
Esler, WP;Stimson, ER;Maggio, JE
通讯作者：
Maggio, JE
影响因子：
5.6
作者：
Cabriolu, Raffaele;Auer, Stefan
通讯作者：
Auer, Stefan
影响因子：
2.9
作者：
Dinkel, Paul D.;Siddiqua, Ayisha;Margittai, Martin
通讯作者：
Margittai, Martin
影响因子：
6.8
作者：
Eliezer, David
通讯作者：
Eliezer, David
DOI：
10.1073/pnas.82.15.5000
发表时间：
1985-01-01
影响因子：
11.1
作者：
ANSARI, A;BERENDZEN, J;YOUNG, RD
通讯作者：
YOUNG, RD