Zα domain proteins mediate the immune response
The Zα domain has a compact α/β architecture containing a three-helix bundle flanked on one side by a twisted antiparallel β sheet. This domain displays a specific affinity for double-stranded nucleic acids that adopt a left-handed helical conformation. Currently, only three Zα-domain proteins have...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1241694/full |
| _version_ | 1827819911271940096 |
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| author | Yuhan Zhong Xiao Zhong Xiao Zhong Liangjun Qiao Hong Wu Chang Liu Ting Zhang |
| author_facet | Yuhan Zhong Xiao Zhong Xiao Zhong Liangjun Qiao Hong Wu Chang Liu Ting Zhang |
| author_sort | Yuhan Zhong |
| collection | DOAJ |
| description | The Zα domain has a compact α/β architecture containing a three-helix bundle flanked on one side by a twisted antiparallel β sheet. This domain displays a specific affinity for double-stranded nucleic acids that adopt a left-handed helical conformation. Currently, only three Zα-domain proteins have been identified in eukaryotes, specifically ADAR1, ZBP1, and PKZ. ADAR1 is a double-stranded RNA (dsRNA) binding protein that catalyzes the conversion of adenosine residues to inosine, resulting in changes in RNA structure, function, and expression. In addition to its editing function, ADAR1 has been shown to play a role in antiviral defense, gene regulation, and cellular differentiation. Dysregulation of ADAR1 expression and activity has been associated with various disease states, including cancer, autoimmune disorders, and neurological disorders. As a sensing molecule, ZBP1 exhibits the ability to recognize nucleic acids with a left-handed conformation. ZBP1 harbors a RIP homotypic interaction motif (RHIM), composed of a highly charged surface region and a leucine-rich hydrophobic core, enabling the formation of homotypic interactions between proteins with similar structure. Upon activation, ZBP1 initiates a downstream signaling cascade leading to programmed cell death, a process mediated by RIPK3 via the RHIM motif. PKZ was identified in fish, and contains two Zα domains at the N-terminus. PKZ is essential for normal growth and development and may contribute to the regulation of immune system function in fish. Interestingly, some pathogenic microorganisms also encode Zα domain proteins, such as, Vaccinia virus and Cyprinid Herpesvirus. Zα domain proteins derived from pathogenic microorganisms have been demonstrated to be pivotal contributors in impeding the host immune response and promoting virus replication and spread. This review focuses on the mammalian Zα domain proteins: ADAR1 and ZBP1, and thoroughly elucidates their functions in the immune response. |
| first_indexed | 2024-03-12T01:20:49Z |
| format | Article |
| id | doaj.art-c68617db9f6d4b3ab04ad35ac86c6d9c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T01:20:49Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c68617db9f6d4b3ab04ad35ac86c6d9c2023-09-13T06:32:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12416941241694Zα domain proteins mediate the immune responseYuhan Zhong0Xiao Zhong1Xiao Zhong2Liangjun Qiao3Hong Wu4Chang Liu5Ting Zhang6Laboratory of Liver Transplantation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Liver Transplantation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaInstitute of Life Sciences, Chongqing Medical University, Chongqing, ChinaInstitute of Life Sciences, Chongqing Medical University, Chongqing, ChinaLaboratory of Liver Transplantation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaDivision of Liver, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Liver Transplantation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaThe Zα domain has a compact α/β architecture containing a three-helix bundle flanked on one side by a twisted antiparallel β sheet. This domain displays a specific affinity for double-stranded nucleic acids that adopt a left-handed helical conformation. Currently, only three Zα-domain proteins have been identified in eukaryotes, specifically ADAR1, ZBP1, and PKZ. ADAR1 is a double-stranded RNA (dsRNA) binding protein that catalyzes the conversion of adenosine residues to inosine, resulting in changes in RNA structure, function, and expression. In addition to its editing function, ADAR1 has been shown to play a role in antiviral defense, gene regulation, and cellular differentiation. Dysregulation of ADAR1 expression and activity has been associated with various disease states, including cancer, autoimmune disorders, and neurological disorders. As a sensing molecule, ZBP1 exhibits the ability to recognize nucleic acids with a left-handed conformation. ZBP1 harbors a RIP homotypic interaction motif (RHIM), composed of a highly charged surface region and a leucine-rich hydrophobic core, enabling the formation of homotypic interactions between proteins with similar structure. Upon activation, ZBP1 initiates a downstream signaling cascade leading to programmed cell death, a process mediated by RIPK3 via the RHIM motif. PKZ was identified in fish, and contains two Zα domains at the N-terminus. PKZ is essential for normal growth and development and may contribute to the regulation of immune system function in fish. Interestingly, some pathogenic microorganisms also encode Zα domain proteins, such as, Vaccinia virus and Cyprinid Herpesvirus. Zα domain proteins derived from pathogenic microorganisms have been demonstrated to be pivotal contributors in impeding the host immune response and promoting virus replication and spread. This review focuses on the mammalian Zα domain proteins: ADAR1 and ZBP1, and thoroughly elucidates their functions in the immune response.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1241694/fullADAR1ZBP1innate immune systemAGScancervirus infection. |
| spellingShingle | Yuhan Zhong Xiao Zhong Xiao Zhong Liangjun Qiao Hong Wu Chang Liu Ting Zhang Zα domain proteins mediate the immune response Frontiers in Immunology ADAR1 ZBP1 innate immune system AGS cancer virus infection. |
| title | Zα domain proteins mediate the immune response |
| title_full | Zα domain proteins mediate the immune response |
| title_fullStr | Zα domain proteins mediate the immune response |
| title_full_unstemmed | Zα domain proteins mediate the immune response |
| title_short | Zα domain proteins mediate the immune response |
| title_sort | zα domain proteins mediate the immune response |
| topic | ADAR1 ZBP1 innate immune system AGS cancer virus infection. |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1241694/full |
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