The Structure and Immune Regulatory Implications of the Ubiquitin-Like Tandem Domain Within an Avian 2'-5' Oligoadenylate Synthetase-Like Protein.
The Structure and Immune Regulatory Implications of the Ubiquitin-Like Tandem Domain Within an Avian 2'-5' Oligoadenylate Synthetase-Like Protein.
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DOI：
10.3389/fimmu.2021.794664
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发表时间：
2021
影响因子：
7.3
通讯作者：
Pegan SD
中科院分区：
文献类型：
--
作者：
Shepard JD;Freitas BT;Rodriguez SE;Scholte FEM;Baker K;Hutchison MR;Longo JE;Miller HC;O'Boyle BM;Tandon A;Zhao P;Grimsey NJ;Wells L;Bergeron É;Pegan SD
泛素和泛素样蛋白对宿主和病毒蛋白的翻译后修饰在宿主产生有效免疫应答的能力中起着关键作用。鸟类物种缺乏在哺乳动物和其他非鸟类爬行动物中发现的泛素样蛋白;干扰素刺激基因产物15（ISG 15）。ISG 15作为信使分子，可以与宿主和病毒蛋白质结合，使其稳定、降解或隔离。在结构上，ISG 15由串联的泛素样结构域（Ubl）组成，其充当翻译后修饰的基序。2 '-5'寡腺苷酸合成酶样蛋白（OASL）还编码两个在其C-末端附近串联的Ubl结构域，其将OASL结合至视黄酸诱导基因-I（RIG-I）。这种蛋白质-蛋白质相互作用增加了RIG-I的敏感性，并导致1型干扰素的产生增强和强大的免疫应答。与人类和其他哺乳动物OASL同源物不同，禽类OASL用泛素和ISG 15中发现的相同LRLRGG基序终止其串联Ubl结构域，所述基序是其与蛋白质缀合所需的基序。然而，鸡缺乏RIG-I，提出了鸡OASL（chOASL）的结构和功能特征的问题。通过研究chOASL，可以探索具有去泛素化酶的病毒的进化历史，并且可以揭示这些病毒的种属特异性的驱动因素。在这里，我们表明chOASL串联Ubl结构域与哺乳动物ISG 15具有相同的结构特征，并且chOASL可以寡聚化并与自身缀合。此外，ISG 15样特征的鸟类OASL，以及它们如何影响与病毒的去泛素化酶和去ISGylases的相互作用进行了探讨。
Post-translational modification of host and viral proteins by ubiquitin and ubiquitin-like proteins plays a key role in a host’s ability to mount an effective immune response. Avian species lack a ubiquitin-like protein found in mammals and other non-avian reptiles; interferon stimulated gene product 15 (ISG15). ISG15 serves as a messenger molecule and can be conjugated to both host and viral proteins leading them to be stabilized, degraded, or sequestered. Structurally, ISG15 is comprised of a tandem ubiquitin-like domain (Ubl), which serves as the motif for post-translational modification. The 2’-5’ oligoadenylate synthetase-like proteins (OASL) also encode two Ubl domains in series near its C-terminus which binds OASL to retinoic acid inducible gene-I (RIG-I). This protein-protein interaction increases the sensitivity of RIG-I and results in an enhanced production of type 1 interferons and a robust immune response. Unlike human and other mammalian OASL homologues, avian OASLs terminate their tandem Ubl domains with the same LRLRGG motif found in ubiquitin and ISG15, a motif required for their conjugation to proteins. Chickens, however, lack RIG-I, raising the question of structural and functional characteristics of chicken OASL (chOASL). By investigating chOASL, the evolutionary history of viruses with deubiquitinases can be explored and drivers of species specificity for these viruses may be uncovered. Here we show that the chOASL tandem Ubl domains shares structural characteristics with mammalian ISG15, and that chOASL can oligomerize and conjugate to itself. In addition, the ISG15-like features of avian OASLs and how they impact interactions with viral deubiquitinases and deISGylases are explored.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.4269/ajtmh.1975.24.1010
发表时间：
1975-01-01
影响因子：
3.3
作者：
CONVERSE, JD;HOOGSTRAAL, H;KAISER, MN
通讯作者：
KAISER, MN
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
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通讯作者：
Zwart PH
影响因子：
5.6
作者：
Daczkowski CM;Dzimianski JV;Clasman JR;Goodwin O;Mesecar AD;Pegan SD
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影响因子：
5.4
作者：
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通讯作者：
Barik, Sailen