摘要
淀粉样纤维是一种高度有序的蛋白聚集体，富含β折叠的结构，具有较强的抗蛋白酶K消化能力，并且可被刚果红染色而呈现出特定的黄绿色双折光。已发现人类大约有20种疾病与淀粉样纤维的沉积有关，如可传播性海绵状脑病(transmissible spongiform encephalopathy，TSE)、阿兹海默病(Alzheimer's disease)、系统性淀粉样变等等，对于这些疾病目前尚无有效的治疗手段。因此，淀粉样变机制的阐明，对于这些疾病的治疗和预防均具有重要的科学意义和应用价值，但目前淀粉样纤维的形成机制仍不清楚。
非染色体遗传原件[URE3]和[PSI~+]分别是酿酒酵母中Ure2p和Sup35p的朊病毒形式。之所以被称为“酵母朊病毒”(yeast prion)，是因为它们的增殖方式与哺乳动物朊病毒非常相似。[URE3]和[PSI~+]的产生分别是由Ure2p和Sup35p发生聚集形成具有自我增殖(selfpropagating)功能的淀粉样物质的结果。因此，酵母朊病毒为研究淀粉样纤维的形成以及朊病毒样的构象转变均提供了一个极有价值的模型。酵母Sup35p是一个蛋白翻译终止因子的亚单位，类似于真核细胞释放因子3(eRF3)。它由685个氨基酸组成，其结构可以划分为3个区。N端区(N，1～123位氨基酸)是酵母形成[PSI~+]所必需的，因此也称为朊病毒结构域(prion domain，PrD)。PrD可以维持酵母[PSI~+]的增殖，而且在体外环境中很容易聚集形成淀粉样纤维。中间区(M，124～253位氨基酸)带有大量的电荷，其功能还不是很清楚。C端区(C，254～685位氨基酸)
Amyloid fibrils are highly ordered protein aggregates characterized by high β-sheet content, protease-resistance, and apple green birefringence on staining with Congo red. Its formation and deposition has been linked to about 20 important human degenerative diseases, including transmissible spongiform encephalopathie (TSE), Alzheimer's disease and systemic amyloidosis. All these diseases lack presently effective treatment and prevention. It is therefore critical to elucidate the mechanisms by which the amyloid fibrils generate and spread to provide targets for diasese treatment and prevention strategy development.
The nonchromosomal genetic elements [URE3] and [PSI~+] are prion forms of the Saccharomyces Cerevisiae proteins Ure2p and Sup35p, respectively. They are called "yeast prions" because of the similarity between their proposed mechanisms of propagation and that of TSE. Both [URE3] and [PSI~+] arise as a consequence of self propagating polymerization of their protein determintants into amyloid-like aggregates. Therefore, yeast prions offer a useful model for studying not only the amyloid formation but also the prion-like transmission of protein conformation. Sup35p is now known to be the yeast homologue of the eukaryotic release factor 3 (eRF3). It functions together with another protein Sup45p to bring about the faithful termination of translation at all three nonsense codons. The Sup35p is composed of three domains. The N-terminal region (amino acids 1-123) constitutes the prion domain (PrD), which is required for induction and maintenance of [PSI~+]. The C-terminal (amino acids 254-685) region contains 4 GTP-binding sites and
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