Structural Basis of RACK7 PHD Domain to Read a Pediatric Glioblastoma-Associated Histone Mutation H3.3G34R

作     者：Wenxian Lan Ze Li Fangfang Jiao Chunxi Wang Rui Guo Chunyang Cao Wenxian Lan;Ze Li;Fangfang Jiao;Chunxi Wang;Rui Guo;Chunyang Cao

作者机构：State Key Laboratory of Bioorganic and Natural Product ChemistryCenter for Excellence in Molecular SynthesisShanghai Institute of Organic ChemistryChinese Academy of Sciences345 Ungling RoadShanghai 200032China Fudan University Shanghai Cancer CenterInstitute of Biomedical SciencesState Key Laboratory of Genetic Engineering and Shanghai Key Laboratory of Medical EpigeneticsShanghai Medical College of Fudan UniversityShanghai 200032China Center for Medical Research and InnovationShanghai Pudong HospitalFudan UniversityPudong Medical Centerand the Shanghai Key Laboratory of Medical Epigeneticsthe International Co-laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyInstitutes of Biomedical SciencesFudan UniversityShanghai 200032China University of Chinese Academy of ScienceNo.19AYuquan RoadShijingshan DistrictBeijing 100049China 

出 版 物：《Chinese Journal of Chemistry》 (中国化学（英文版）)

年 卷 期：2021年第39卷第9期

页      面：2433-2440页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071007[理学-遗传学] 

基　　金：supported by the National Program on the Key Basic Research Project of China(Nos.2017YFE0108200,2018YFA0108700,2016YFA0502302 and 2016YFA0500700) by NSFC(Nos.21807105,91753119,21977110,31571318,21778065 and 31771450) by the Strategic Priority Research Program,CAS(No.XDB 20000000) by Center for Excellence in Molecular Synthesis,CAS(No.FZHCZY020600) 

主　　题：RACK7 H3.3G34R Interaction NMR Structure 

摘      要：Histone point mutations,including missense mutations on histone H3 at positions 27(K27M),34(G34R/V,G34W,G34L)and 36(K36M),were identified as potential cancer driver mutations.H3.3G34R/V mutations account for pediatric glioblastomas(GBM).RACK7(also known as ZMYND8,PRKCBP1)was recently reported to specifically bind H3.3G34R through its PHD(plant homedomain)domain(PHDRACK7)in vitro and in H3.3G34R pediatric glioblastoma cells,playing key roles in H3.3G34R-mediated gene ***,we provided both biochemical and NMR structural evidences that PHDRACK7 recognized histone H3.3G34R mutant via a mechanism distinet from all other reported PHD *** the reported residue D104,two new sites D108 and L121 of PHD^(RACK7) were found necessary for the interactions between PHD^(RACK7) and histone H3.3G34R *** results provided a potential molecular basis for pediatric GBM driven by the H3.3G34R mutation.