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从一位多发性硬化症患者中分离出的质粒编码的复制蛋白的结构分析。

Structural analysis of a replication protein encoded by a plasmid isolated from a multiple sclerosis patient.

机构信息

Schaller Research Group at the University of Heidelberg, Heidelberg, Germany.

Structural Biology Group, European Synchrotron Radiation Facility (ESRF), Grenoble, France.

出版信息

Acta Crystallogr D Struct Biol. 2019 May 1;75(Pt 5):498-504. doi: 10.1107/S2059798319003991. Epub 2019 Apr 29.

DOI:10.1107/S2059798319003991
PMID:31063152
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6503762/
Abstract

Bovine meat and milk factors (BMMFs) are circular, single-stranded episomal DNAs that have been detected in bovine meat and milk products. BMMFs are thought to have roles in human malignant and degenerative diseases. BMMFs encode a replication initiator protein (Rep) that is actively transcribed and translated in human cells. In this study, a Rep WH1 domain encoded on a BMMF (MSBI1.176) isolated from a multiple sclerosis human brain sample was determined to 1.53 Å resolution using X-ray crystallography. The overall structure of the MSBI1.176 WH1 domain was remarkably similar to other Rep structures, despite having a low (28%) amino-acid sequence identity. The MSBI1.176 WH1 domain contained elements common to other Reps, including five α-helices, five β-strands and a hydrophobic pocket. These new findings suggest that the MSBI1.176 Rep might have comparable roles and functions to other known Reps of different origins.

摘要

牛肌肉和牛奶因子（BMMFs）是在牛肌肉和奶制品中检测到的圆形、单链环状外源性 DNA。BMMFs 被认为在人类恶性和退行性疾病中发挥作用。BMMFs 编码一种复制起始蛋白（Rep），在人类细胞中被积极转录和翻译。在这项研究中，使用 X 射线晶体学确定了从多发性硬化症人类脑组织样本中分离出的 BMMF（MSBI1.176）上编码的 Rep WH1 结构域的分辨率为 1.53 Å。尽管 MSBI1.176 WH1 结构域的氨基酸序列同一性较低（28%），但其整体结构与其他 Rep 结构非常相似。MSBI1.176 WH1 结构域包含与其他 Rep 共有的元件，包括五个α-螺旋、五个β-链和一个疏水性口袋。这些新发现表明，MSBI1.176 Rep 可能具有与其他来源不同的已知 Rep 相当的作用和功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c605/6503762/31c3c67df6d9/d-75-00498-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c605/6503762/8a2cbb35fdf6/d-75-00498-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c605/6503762/b5d4b132724c/d-75-00498-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c605/6503762/db5365cf0498/d-75-00498-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c605/6503762/0296f0969891/d-75-00498-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c605/6503762/31c3c67df6d9/d-75-00498-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c605/6503762/8a2cbb35fdf6/d-75-00498-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c605/6503762/b5d4b132724c/d-75-00498-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c605/6503762/db5365cf0498/d-75-00498-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c605/6503762/0296f0969891/d-75-00498-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c605/6503762/31c3c67df6d9/d-75-00498-fig5.jpg

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本文引用的文献

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Int J Cancer. 2019 Apr 1;144(7):1574-1583. doi: 10.1002/ijc.31882. Epub 2018 Dec 6.
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Addressing Intracellular Amyloidosis in Bacteria with RepA-WH1, a Prion-Like Protein.利用类朊病毒蛋白RepA-WH1解决细菌中的细胞内淀粉样变性问题。
Methods Mol Biol. 2018;1779:289-312. doi: 10.1007/978-1-4939-7816-8_18.
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Expression and replication of virus-like circular DNA in human cells.
从牛血清、乳制品和癌旁结肠组织中分离出的一类特定的传染性病原体。
Emerg Microbes Infect. 2019;8(1):1205-1218. doi: 10.1080/22221751.2019.1651620.
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Isolation of Two Virus-Like Circular DNAs from Commercially Available Milk Samples.从市售牛奶样本中分离出两种病毒样环状DNA。
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