Zα domain proteins mediate the immune response

作者全名："Zhong, Yuhan; Zhong, Xiao; Qiao, Liangjun; Wu, Hong; Liu, Chang; Zhang, Ting"

作者地址："[Zhong, Yuhan; Zhong, Xiao; Wu, Hong; Zhang, Ting] Sichuan Univ, West China Hosp, Frontiers Sci Ctr Dis Related Mol Network, Lab Liver Transplantat, Chengdu, Peoples R China; [Zhong, Xiao; Qiao, Liangjun] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China; [Liu, Chang] Sichuan Univ, West China Hosp, Dept Gen Surg, Div Liver, Chengdu, Peoples R China"

通信作者："Zhang, T (通讯作者)，Sichuan Univ, West China Hosp, Frontiers Sci Ctr Dis Related Mol Network, Lab Liver Transplantat, Chengdu, Peoples R China.; Liu, C (通讯作者)，Sichuan Univ, West China Hosp, Dept Gen Surg, Div Liver, Chengdu, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001074813200001

JCR分区：Q1

影响因子：5.7

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Review

关键词：ADAR1; ZBP1; innate immune system; AGS; cancer; virus infection.

摘要："The Z alpha domain has a compact alpha/beta architecture containing a three-helix bundle flanked on one side by a twisted antiparallel beta sheet. This domain displays a specific affinity for double-stranded nucleic acids that adopt a left-handed helical conformation. Currently, only three Z alpha-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 Z alpha 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 Z alpha domain proteins, such as, Vaccinia virus and Cyprinid Herpesvirus. Z alpha 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 Z alpha domain proteins: ADAR1 and ZBP1, and thoroughly elucidates their functions in the immune response."

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