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疾病相关朊病毒纤维的冷冻电镜结构为研究引发障碍提供了线索。

Cryo-EM structure of disease-related prion fibrils provides insights into seeding barriers.

机构信息

Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA.

Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.

出版信息

Nat Struct Mol Biol. 2022 Oct;29(10):962-965. doi: 10.1038/s41594-022-00833-4. Epub 2022 Sep 12.

DOI:10.1038/s41594-022-00833-4
PMID:36097290
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9639217/
Abstract

One of the least understood aspects of prion diseases is the structure of infectious prion protein aggregates. Here we report a high-resolution cryo-EM structure of amyloid fibrils formed by human prion protein with the Y145Stop mutation that is associated with a familial prion disease. This structural insight allows us not only to explain previous biochemical findings, but also provides direct support for the conformational adaptability model of prion transmissibility barriers.

摘要

朊病毒疾病中最不为人理解的方面之一是传染性朊病毒蛋白聚集体的结构。在这里，我们报告了由与家族性朊病毒疾病相关的 Y145Stop 突变的人朊病毒蛋白形成的淀粉样纤维的高分辨率冷冻电镜结构。这一结构上的认识不仅使我们能够解释以前的生化发现，而且还为朊病毒传播障碍的构象适应性模型提供了直接支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/36485f6aa863/nihms-1833075-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/5a4335659274/nihms-1833075-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/31d9f5550597/nihms-1833075-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/a56b67921742/nihms-1833075-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/c75cb0af6887/nihms-1833075-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/8c5faecdc52e/nihms-1833075-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/c44ebc08cb4f/nihms-1833075-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/c782eacd643f/nihms-1833075-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/ba77ce05be3b/nihms-1833075-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/201aef403899/nihms-1833075-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/36485f6aa863/nihms-1833075-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/5a4335659274/nihms-1833075-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/31d9f5550597/nihms-1833075-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/a56b67921742/nihms-1833075-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/c75cb0af6887/nihms-1833075-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/8c5faecdc52e/nihms-1833075-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/c44ebc08cb4f/nihms-1833075-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/c782eacd643f/nihms-1833075-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/ba77ce05be3b/nihms-1833075-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/201aef403899/nihms-1833075-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce0d/9639217/36485f6aa863/nihms-1833075-f0002.jpg

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本文引用的文献

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Genetic prion disease-related mutation E196K displays a novel amyloid fibril structure revealed by cryo-EM.与遗传性朊病毒病相关的突变E196K呈现出一种由冷冻电镜揭示的新型淀粉样纤维结构。
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High-resolution structure and strain comparison of infectious mammalian prions.传染性哺乳动物朊病毒的高分辨率结构和应变比较。
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