神经内分泌特异的转录因子INSM1是调控神经内分泌系统发育的关键蛋白，与多种神经内分泌肿瘤的形成有关。INSM1蛋白含有5个C2H2型锌指（ZF1-5），识别一种与现有理论模型预测结果显著不同的保守DNA基序，是INSM1转录调控功能的前提基础。目前，还缺乏关于这些锌指的结构和其与DNA互作机制的研究，制约着对INSM1功能分子机理的认识。本项目计划利用核磁共振（NMR）等方法，解析含有在DNA结合中起主要作用的ZF2和ZF3的INSM1截短蛋白（ZF1-3）的溶液结构，分析其寡聚状态，揭示寡聚物形成的机制及对DNA结合功能的影响，并通过NMR滴定等方法鉴定结合DNA的关键残基。研究成果将首次报道INSM1蛋白的二聚化，帮助我们理解INSM1如何形成二聚体和识别特殊的DNA基序，完善现有锌指蛋白-DNA识别模型，还可能为研发药物分子通过改变INSM1寡聚状态以调控其细胞内功能提供依据。

INSM1, a neuroendocrine-specific transcription factor playing a vital role in the development of neuroendocrine system, has been implicated in the formation of various neuroendocrine tumors. INSM1 employs its C-terminal five C2H2 zinc fingers (ZF1-5) as the functional basis for transcriptional regulation, which recognize a consensus DNA motif different from the one predicted according to current available DNA recognizing model of C2H2 zinc finger. So far, there is neither solved structure of these ZFs, nor the study on how these ZFs interact with the special consensus DNA. In this project, ZF1-3, a truncated version of INSM1 containing ZF1, ZF2 and ZF3, with the latter two having been suggested to play a major role in DNA binding, will be studied. we will characterize the dimerization state of ZF1-3 and solve its solution structure using NMR spectroscopy，to find out how ZF1-3 dimerizes and the role of dimerization on DNA binding. Further, we will try to identify the key residues of ZF1-3 for DNA binding using methods including NMR titration. Our study will report the dimerization of INSM1 for the first time, reveal the mechanism of INSM1 binding with its consensus DNA, improve general DNA recognizing model of C2H2 zinc finger, and provide useful informations for the design of molecules modulating the dimerization of INSM1 and thereby the function of INSM1 in cells.