The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development  

作　　者：Xiaozhen Song Ruixing Hu Yi Chen Man Xiao Hong Zhang Shengnan Wu Qing Lu 

机构地区：[1]Molecular Diagnostic Laboratory,Shanghai Children’s Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200040,China [2]Bio-X Institutes,Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education),Shanghai Jiao Tong University,Shanghai 200030,China [3]Laboratory of Development and Diseases and State Key Laboratory for Medical Genomics,Shanghai Institute of Hematology,Ruijin Hospital,Shanghai JiaoTong University School of Medicine,Shanghai 200025,China

出　　处：《Journal of Molecular Cell Biology》2024年第1期43-53,共11页分子细胞生物学报（英文版）

基　　金：funded by Shanghai Jiao Tong University‘Star of Jiao Tong University’Medical-Engineering Cross Research Fund(YG2019QNB01);Shanghai Municipal Key Clinical Specialty(shslczdzk06902);Shanghai Children's Hospital Fund(2022YGZM01).

摘　　要：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 3.3Åresolution 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.

关 键 词：TRAF7 coiled-coil domain crystal structure TRIMERIZATION embryonic development 

分 类 号：Q78[生物学—分子生物学]