Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
Mol Microbiol. 2019 Mar;111(3):798-810. doi: 10.1111/mmi.14192. Epub 2019 Feb 1.
[PSI ] variants are different infectious conformations of the same Sup35 protein. We show that when [PSI ] variants VK and VL co-infect a dividing host, only one prevails in the end and the host genetic background is involved in winner selection. In the 5V-H19 background, the VK variant dominates over the VL variant. The order of dominance is reversed in the 74-D694 background, where VL can coexists with VK for a short period, but will eventually take over. Differential interaction of chaperone proteins with distinct prion variant conformations can influence the outcome of competition. Expanding the Glycine/Methionine-rich domain of Sis1, an Hsp40 protein, helps the propagation of VL. Over-expression of the Hsp70 protein Ssa2 lowers the number of prion particles (propagons) in the cell. There is more reduction for VK than VL, causing the latter to dominate in some of the 5V-H19 and all of the 74-D694 cells tested. Consistently, depleting Ssa1 in 74-D694 strengthens VK. Swapping chromosomal alleles of SSA1/2 and SIS1 between 5V-H19 and 74-D694, including cognate promoters, is not sufficient to change the native dominance order of each background, suggesting there exist additional polymorphic factors that modulate [PSI ] competition.
PSI 变体是同一种 Sup35 蛋白的不同感染构象。我们表明，当 [PSI ] 变体 VK 和 VL 共同感染一个分裂的宿主时，最终只有一种变体占优势，而宿主的遗传背景参与了胜者的选择。在 5V-H19 背景下，VK 变体占优势于 VL 变体。在 74-D694 背景下，优势顺序相反，VL 可以与 VK 短时间共存，但最终会接管。伴侣蛋白与不同朊病毒变体构象的不同相互作用可以影响竞争的结果。扩展 Hsp40 蛋白 Sis1 的甘氨酸/蛋氨酸丰富结构域有助于 VL 的传播。Hsp70 蛋白 Ssa2 的过表达会降低细胞中朊病毒颗粒（传播子）的数量。对于 VK 的减少比 VL 更多，导致后者在一些 5V-H19 和所有 74-D694 细胞中占优势。一致地，在 74-D694 中耗尽 Ssa1 会增强 VK。在 5V-H19 和 74-D694 之间交换 SSA1/2 和 SIS1 的染色体等位基因，包括同源启动子，不足以改变每个背景的固有优势顺序，表明存在额外的多态因素来调节 [PSI ] 竞争。
