Xiaozhen Song, Ruixing Hu, Yi Chen, Man Xiao, Hong Zhang, Shengnan Wu, Qing Lu
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引用次数: 0
摘要
TRAF7是一种重要的细胞内适配体和E3泛素连接酶,参与信号转导通路,对免疫反应、肿瘤进展和胚胎发育做出了贡献。TRAF7的盘绕线圈(CC)结构域和WD40重复结构域的体细胞突变可导致脑肿瘤,而种系致病突变则会导致严重的发育异常。然而,TRAF7参与胚胎发育的确切分子机制仍不清楚。在本研究中,我们采用斑马鱼作为体内模型系统。敲除 TRAF7 会导致斑马鱼胚胎发育缺陷。我们以 3.3 Å 的分辨率测定了 TRAF7 CC 结构域的晶体结构,发现在斑马鱼胚胎发育过程中,CC 区域的三聚体化对 TRAF7 的功能至关重要。此外,TRAF7 CC区的致病突变会影响三聚体的形成,从而影响斑马鱼早期胚胎发育。因此,我们的研究揭示了TRAF7 CC三聚体形成的分子机制及其在胚胎发育中的关键作用。
The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development.
TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways, contributing to immune responses, tumor progression, and embryonic development. Somatic mutations within the coiled-coil (CC) domain and WD40 repeat domain of TRAF7 could cause brain tumors, while germline pathogenic mutations contribute to severe developmental abnormalities. However, the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains unclear. In this study, we employed zebrafish as an in vivo model system. TRAF7 knock down caused defects in zebrafish embryonic development. We determined the crystal structure of TRAF7 CC domain at 3.3 Å resolution and found that the CC region trimerization was essential for TRAF7 functionality during zebrafish embryonic development. Additionally, disease-causing mutations in TRAF7 CC region could impair the trimer formation, consequently impacting early embryonic development of zebrafish. Therefore, our study sheds light on the molecular mechanism of TRAF7 CC trimer formation and its pivotal role in embryonic development.
期刊介绍:
The Journal of Molecular Cell Biology ( JMCB ) is a full open access, peer-reviewed online journal interested in inter-disciplinary studies at the cross-sections between molecular and cell biology as well as other disciplines of life sciences. The broad scope of JMCB reflects the merging of these life science disciplines such as stem cell research, signaling, genetics, epigenetics, genomics, development, immunology, cancer biology, molecular pathogenesis, neuroscience, and systems biology. The journal will publish primary research papers with findings of unusual significance and broad scientific interest. Review articles, letters and commentary on timely issues are also welcome.
JMCB features an outstanding Editorial Board, which will serve as scientific advisors to the journal and provide strategic guidance for the development of the journal. By selecting only the best papers for publication, JMCB will provide a first rate publishing forum for scientists all over the world.