Distinct Subregions of Swi1 Manifest Striking Differences in Prion Transmission and SWI/SNF Function
Distinct Subregions of Swi1 Manifest Striking Differences in Prion Transmission and SWI/SNF Function
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DOI：
10.1128/mcb.00225-10
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发表时间：
2010-10-01
影响因子：
5.3
通讯作者：
Li, Liming
中科院分区：
文献类型：
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作者：
Du, Zhiqiang;Crow, Emily T.;Li, Liming
我们最近报道，酵母染色质重塑因子Swi 1可以作为朊病毒存在，[SWI+]，证明朊病毒发生和全球转录调控之间的联系。为了阐明Swi 1构象开关如何影响Swi 1功能，并定义[SWI+]形成和传播的序列和结构要求，我们从功能上解剖了Swi 1分子。我们在这里表明，[SWI+]朊病毒的特点是完全归因于前327个氨基酸残基（N），是天冬酰胺丰富的区域。N在[SWI+]细胞中聚集，但在[swi（-）]细胞中扩散; N编码区的染色体缺失导致[SWI+]丢失，重组N肽能够在体外形成感染性淀粉样纤维，通过简单的转化使[SWI+]从头形成。虽然富含谷氨酰胺的中间区域（Q）不足以在[SWI+]细胞中聚集或对SWI/SNF功能至关重要，但它显著改变了Swi 1聚集模式和Swi 1功能。我们还表明，过多的Swi 1引起Li+/Na+的敏感性和N/Q区域是重要的，这种增益的敏感性。总之，我们的研究结果提供了最终的证据，“蛋白质”传输的[SWI+]，并表明，广泛分布的“非”谷氨酰胺/天冬酰胺丰富的区域/基序可能具有重要的和不同的生物学功能。
We have recently reported that the yeast chromatin-remodeling factor Swi1 can exist as a prion, [SWI+], demonstrating a link between prionogenesis and global transcriptional regulation. To shed light on how the Swi1 conformational switch influences Swi1 function and to define the sequence and structural requirements for [SWI+] formation and propagation, we functionally dissected the Swi1 molecule. We show here that the [SWI+] prion features are solely attributable to the first 327 amino acid residues (N), a region that is asparagine rich. N was aggregated in [SWI+] cells but diffuse in [swi(-)] cells; chromosomal deletion of the N-coding region resulted in [SWI+] loss, and recombinant N peptide was able to form infectious amyloid fibers in vitro, enabling [SWI+] de novo formation through a simple transformation. Although the glutamine-rich middle region (Q) was not sufficient to aggregate in [SWI+] cells or essential for SWI/SNF function, it significantly modified the Swi1 aggregation pattern and Swi1 function. We also show that excessive Swi1 incurred Li+/Na+ sensitivity and that the N/Q regions are important for this gain of sensitivity. Taken together, our results provide the final proof of "protein-only" transmission of [SWI+] and demonstrate that the widely distributed "dispensable" glutamine/asparagine-rich regions/motifs might have important and divergent biological functions.