Two structurally similar fungal prions efficiently cross-seed in vivo but form distinct polymers when coexpressed
Two structurally similar fungal prions efficiently cross-seed in vivo but form distinct polymers when coexpressed
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DOI：
10.1111/j.1365-2958.2011.07893.x
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发表时间：
2011-12-01
影响因子：
3.6
通讯作者：
Saupe, Sven J.
中科院分区：
文献类型：
--
作者：
Benkemoun, Laura;Ness, Frederique;Saupe, Sven J.
HET-s是丝状真菌鹅柄孢菌的一种朊病毒蛋白。这种蛋白质的直向同源物称为FgHET-s，已在禾谷镰刀菌中鉴定。FgHET-s蛋白的对应于HET-s的朊病毒形成结构域的区域在体外形成淀粉样原纤维。这些原纤维在体外播种HET-s（218289）原纤维形成，反之亦然。HET-s（218289）和FgHET-s（218289）的淀粉样蛋白折叠非常相似，尽管它们仅具有38%的同一性。本工作对应于FgHET-s（218289）区域作为体内朊病毒形成结构域的功能表征。我们表明FgHET-s（218289）能够在鹅绒委陵菜中增殖朊病毒，并且能够替代全长HET-s蛋白中的HET-s PFD。通过体外交叉播种实验，我们发现在鹅绒委陵菜和F.禾谷早熟禾PFDs.我们使用酵母酿酒酵母作为宿主，比较两个orthopulmonary PFDs的朊病毒性能。我们发现FgHET-s（218289）导致比HET-s（218289）更高的自发朊病毒形成率和有丝分裂朊病毒稳定性。然后分析HET-s（218289）/FgHET-s（218289）共表达的结果。尽管HET-s（218289）和FgHET-s（218289）具有交叉接种能力，但在体内，同型聚合优于混合原纤维形成。
HET-s is a prion protein of the filamentous fungus Podospora anserina. An orthologue of this protein, called FgHET-s has been identified in Fusarium graminearum. The region of the FgHET-s protein corresponding to the prion forming domain of HET-s, forms amyloid fibrils in vitro. These fibrils seed HET-s(218289) fibril formation in vitro and vice versa. The amyloid fold of HET-s(218289) and FgHET-s(218289) are remarkably similar although they share only 38% identity. The present work corresponds to the functional characterization of the FgHET-s(218289) region as a prion forming domain in vivo. We show that FgHET-s(218289) is capable of prion propagation in P. anserina and is able to substitute for the HET-s PFD in the full-length HET-s protein. In accordance with the in vitro cross-seeding experiments, we detect no species barrier between P. anserina and F. graminearum PFDs. We use the yeast Saccharomyces cerevisiae as a host to compare the prion performances of the two orthologous PFDs. We find that FgHET-s(218289) leads to higher spontaneous prion formation rates and mitotic prion stability than HET-s(218289). Then we analysed the outcome of HET-s(218289)/FgHET-s(218289) coexpression. In spite of the cross-seeding ability of HET-s(218289) and FgHET-s(218289), in vivo, homotypic polymerization is favoured over mixed fibril formation.