人体内转录因子Sry-related Box 17 结合DNA反应机理的结构生物学研究（可编辑）【大学毕业论文】.docVIP

人体内转录因子Sry-related Box 17 结合DNA反应机理的结构生物学研究 5 10 15 20 25 30 35 40 中国医学科学院北京协和医学院药用植物研究所北京 100193 摘要Sry-related Box 简称 Sox 是一类含有一个 HMG 结构域的转录因子HMG 结构域结 合 DNA 后使 DNA 发生弯曲从而达到调控遗传信息转录的效果在器官分化期各个 Sox 成 员在不同的细胞系中具有不同的转录调控功能表明每种 Sox 转录因子具有其独特的与 DNA 相互作用的机理研究每种 Sox 转录因子的 HMG 结构域与 DNA 结合前后空间结构变 化可以为阐明 Sox 转录因子各自不同的 DNA 结合机理提供分子结构证据之前的研究报道 了 Sox2Sox4Sox9Sox17 的 HMG 结构域与 DNA 复合体的晶体结构但缺乏测定对应 的 HMG 结构域单体的晶体结构来证明 DNA 结合后 HMG 结构域的空间结构变化为了填 补这些对自然现象理解的不足之处本研究测定了 24 分辨率 Sox17 的 HMG 结构域的晶 体结构从分子结构层面阐明了 Sox17 与 DNA 的相互作用机理 关键词转录因子Sry-related Box 17 Sox17 HMG 结构域DNA 结合晶体结构 中图分类号Q512 Structure Biological Investigation of Human Transcription Factor Sry-related Box 17 Binding to DNA REN Jixia XIE Yong Institute of Medicinal Plant Development Chinese Academy of Medical Science Peking Union Medical College Beijing 100193 Abstract Sry-related box Sox transcription factors share a conserved high-mobility-group box domain HMG-domain that binds DNA and bends DNA for further assembly of transcriptional machineries During organogenesis each member of the Sox family triggers a specific cell lineage differentiation indicating that their interactions with DNA are different from each other Investigating structural rearrangement of each Sox transcription factor HMG-domain upon binding to DNA would help to elucidate the distinctive molecular mechanism by which they interact with DNA Previous studies have determined the crystal structures of Sox2 HMG-domainDNA Sox4 HMG-domainDNA Sox9 HMG-domainDNA and Sox17 HMG-domainDNA complexes However major gaps remain in the structural information on the Sox transcription factor HMG-domains Here we report the crystal structure of the human Sox17 HMG-domain alone at 24 resolution Comparing this structure and the structure of the Sox17 HMG-domainDNA complex provides structural evidence to understand how to Sox17 binding to DNA Keywords Transcription factor sry-related box 17 Sox17 HMG-domain crystal structure DNA-binding 0 引言 转录因子是一类通过识别 DNA 分子 5端特定