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缓步动物损伤抑制蛋白（Dsup）的内在无序结构研究及其与DNA的复合物。

Structural study of the intrinsically disordered tardigrade damage suppressor protein (Dsup) and its complex with DNA.

作者信息

Zarubin Mikhail, Murugova Tatiana, Ryzhykau Yury, Ivankov Oleksandr, Uversky Vladimir N, Kravchenko Elena

机构信息

Dzhelepov Laboratory of Nuclear Problems, Joint Institute for Nuclear Research, Dubna, Russia.

Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna, Russia.

出版信息

Sci Rep. 2024 Oct 2;14(1):22910. doi: 10.1038/s41598-024-74335-2.

DOI:10.1038/s41598-024-74335-2
PMID:39358423
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11447161/
Abstract

Studies of proteins, found in one of the most stress-resistant animals tardigrade Ramazzottius varieornatus, aim to reveal molecular principles of extreme tolerance to various types of stress and developing applications based on them for medicine, biotechnology, pharmacy, and space research. Tardigrade DNA/RNA-binding damage suppressor protein (Dsup) reduces DNA damage caused by reactive oxygen spices (ROS) produced upon irradiation and oxidative stresses in Dsup-expressing transgenic organisms. This work is focused on the determination of structural features of Dsup protein and Dsup-DNA complex, which refines details of protective mechanism. For the first time, intrinsically disordered nature of Dsup protein with highly flexible structure was experimentally proven and characterized by the combination of small angle X-ray scattering (SAXS) technique, circular dichroism spectroscopy, and computational methods. Low resolution models of Dsup protein and an ensemble of conformations were presented. In addition, we have shown that Dsup forms fuzzy complex with DNA.

摘要

对发现于最具抗逆性的动物之一水熊虫（Ramazzottius varieornatus）体内的蛋白质进行研究，旨在揭示其对各种类型压力具备极端耐受性的分子原理，并在此基础上开发适用于医学、生物技术、制药和太空研究的应用。水熊虫DNA/RNA结合损伤抑制蛋白（Dsup）可减少在表达Dsup的转基因生物中，由辐射和氧化应激产生的活性氧（ROS）所导致的DNA损伤。这项工作聚焦于确定Dsup蛋白和Dsup-DNA复合物的结构特征，从而完善保护机制的细节。首次通过小角X射线散射（SAXS）技术、圆二色光谱和计算方法相结合，实验证明并表征了Dsup蛋白具有高度灵活结构的内在无序性质。给出了Dsup蛋白的低分辨率模型和一系列构象。此外，我们还表明Dsup与DNA形成模糊复合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/acc381923ab9/41598_2024_74335_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/b756c0545c64/41598_2024_74335_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/a2ecdce3c36d/41598_2024_74335_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/c70c77266e95/41598_2024_74335_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/b5b368d7ff6d/41598_2024_74335_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/8d652d092cf6/41598_2024_74335_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/79fa523a9b4d/41598_2024_74335_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/71b9c9f1001e/41598_2024_74335_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/acc381923ab9/41598_2024_74335_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/b756c0545c64/41598_2024_74335_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/a2ecdce3c36d/41598_2024_74335_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/c70c77266e95/41598_2024_74335_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/b5b368d7ff6d/41598_2024_74335_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/8d652d092cf6/41598_2024_74335_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/79fa523a9b4d/41598_2024_74335_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/71b9c9f1001e/41598_2024_74335_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39ee/11447161/acc381923ab9/41598_2024_74335_Fig8_HTML.jpg

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