National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Prion. 2010 Jan-Mar;4(1):9-12. doi: 10.4161/pri.4.1.10670. Epub 2010 Jan 16.
Our laboratory recently reported the identification of a peptide region, QVNI, within the prion domain of the yeast protein Ure2 that may act as an initiation point for fibril formation.(1) This potential amyloid-forming region, which corresponds to residues 18-21 of Ure2, was initially identified by systematic cysteine scanning of the Ure2 prion domain. The point mutant R17C, and the corresponding octapeptide CQVNIGNR, were found to form fibrils rapidly under oxidative conditions due to the formation of a disulfide bond. Deletions within the QVNI sequence cause the fibril formation ability of R17C Ure2 to be inhibited. The aggregation propensity of this region is strongly modulated by its preceding residue: replacement of R17 with a hydrophobic residue promotes fibril formation in both full-length Ure2 and in the corresponding octapeptides. The wild-type octapeptide, RQVNIGNR, also forms fibrils, and is the shortest amyloid-forming peptide found for Ure2 to date. Interestingly, the wild-type octapeptide crystallizes readily and so provides a starting point towards obtaining high resolution structural information for the amyloid core of Ure2 fibrils.
我们实验室最近报道了酵母蛋白 Ure2 的朊病毒结构域内可能作为纤维形成起始点的肽区域 QVNI 的鉴定。(1) 该潜在的淀粉样形成区域对应于 Ure2 的残基 18-21，最初是通过系统的半胱氨酸扫描 Ure2 朊病毒结构域来鉴定的。点突变 R17C 和相应的八肽 CQVNIGNR 在氧化条件下由于形成二硫键而迅速形成纤维。QVNI 序列内的缺失导致 R17C Ure2 的纤维形成能力受到抑制。该区域的聚集倾向受其前一个残基强烈调节：用疏水性残基替换 R17 可促进全长 Ure2 和相应八肽中的纤维形成。野生型八肽 RQVNIGNR 也形成纤维，是迄今为止在 Ure2 中发现的最短的形成淀粉样纤维的肽。有趣的是，野生型八肽容易结晶，因此为获得 Ure2 纤维的淀粉样核心的高分辨率结构信息提供了一个起点。
