Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0830, USA.
Biochemistry. 2011 Jul 12;50(27):5971-8. doi: 10.1021/bi200142x. Epub 2011 Jun 15.
Ure2p of Candida albicans (Ure2(albicans) or CaUre2p) can be a prion in Saccharomyces cerevisiae, but Ure2p of Candida glabrata (Ure2(glabrata)) cannot, even though the Ure2(glabrata) N-terminal domain is more similar to that of the S. cerevisiae Ure2p (Ure2(cerevisiae)) than Ure2(albicans) is. We show that the N-terminal N/Q-rich prion domain of Ure2(albicans) forms amyloid that is infectious, transmitting [URE3alb] to S. cerevisiae cells expressing only C. albicans Ure2p. Using solid-state nuclear magnetic resonance of selectively labeled C. albicans Ure2p(1-90), we show that this infectious amyloid has an in-register parallel β-sheet structure, like that of the S. cerevisiae Ure2p prion domain and other S. cerevisiae prion amyloids. In contrast, the N/Q-rich N-terminal domain of Ure2(glabrata) does not readily form amyloid, and that formed upon prolonged incubation is not infectious.
白色念珠菌的 Ure2p(Ure2(albicans)或 CaUre2p)可以在酿酒酵母中形成朊病毒,但光滑念珠菌的 Ure2p(Ure2(glabrata))却不能,尽管 Ure2(glabrata)的 N 端结构域与酿酒酵母的 Ure2p(Ure2(cerevisiae))更为相似,而不是与 Ure2(albicans)相似。我们发现,白色念珠菌 Ure2(albicans)的 N 端富含 N/Q 的朊病毒结构域形成的淀粉样纤维具有感染性,可将[URE3alb]传递给仅表达白色念珠菌 Ure2p 的酿酒酵母细胞。通过对选择性标记的白色念珠菌 Ure2p(1-90)进行固态核磁共振分析,我们发现这种具有传染性的淀粉样纤维具有有序平行的β-折叠结构,与酿酒酵母 Ure2p 朊病毒结构域和其他酿酒酵母朊病毒淀粉样纤维相似。相比之下,Ure2(glabrata)富含 N/Q 的 N 端结构域不易形成淀粉样纤维,即使在长时间孵育后形成的淀粉样纤维也没有感染性。