Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830
Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830.
Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):E2711-20. doi: 10.1073/pnas.1409582111. Epub 2014 Jun 17.
[URE3] is an amyloid prion of the Saccharomyces cerevisiae Ure2p, a regulator of nitrogen catabolism. Overproduction of Btn2p, involved in late endosome to Golgi protein transport, or its paralog Cur1p, cures [URE3]. Btn2p, in curing, is colocalized with Ure2p in a single locus, suggesting sequestration of Ure2p amyloid filaments. We find that most [URE3] variants generated in a btn2 cur1 double mutant are cured by restoring normal levels of Btn2p and Cur1p, with both proteins needed for efficient curing. The [URE3] variants cured by normal levels of Btn2p and Cur1p all have low seed number, again suggesting a seed sequestration mechanism. Hsp42 overproduction also cures [URE3], and Hsp42p aids Btn2 overproduction curing. Cur1p is needed for Hsp42 overproduction curing of [URE3], but neither Btn2p nor Cur1p is needed for overproduction curing by the other. Although hsp42Δ strains stably propagate [URE3-1], hsp26Δ destabilizes this prion. Thus, Btn2p and Cur1p are antiprion system components at their normal levels, acting with Hsp42. Btn2p is related in sequence to human Hook proteins, involved in aggresome formation and other transport activities.
[URE3] 是一种淀粉样蛋白朊病毒，来自酿酒酵母 Ure2p，是氮代谢的调控因子。Btn2p（参与晚期内体到高尔基体的蛋白质运输）或其同源物 Cur1p 的过表达可以治愈 [URE3]。在治愈过程中，Btn2p 与 Ure2p 共定位于一个单一的位置，这表明 Ure2p 淀粉样丝被隔离。我们发现，在 btn2 cur1 双突变体中产生的大多数 [URE3] 变体通过恢复正常水平的 Btn2p 和 Cur1p 得到治愈，这两种蛋白都需要高效治愈。通过正常水平的 Btn2p 和 Cur1p 治愈的 [URE3] 变体的种子数都很低，这再次表明存在一种种子隔离机制。Hsp42 的过表达也能治愈 [URE3]，并且 Hsp42p 有助于 Btn2 的过表达治愈。Cur1p 是 Hsp42 过表达治愈 [URE3] 所必需的，但 Cur1p 既不是 Btn2p 也不是 Cur1p 过表达治愈所必需的。尽管 hsp42Δ 菌株稳定地繁殖 [URE3-1]，但 hsp26Δ 会使这种朊病毒不稳定。因此，在正常水平下，Btn2p 和 Cur1p 是抗朊病毒系统的组成部分，与 Hsp42 一起发挥作用。Btn2p 在序列上与人类 Hook 蛋白有关，后者参与聚集体的形成和其他运输活动。
