施一公2014-04-14 5:56 PM

绑定于DNASmad的蛋白MH1域的晶体结构:对TGF-b信号中的DNA结合的见解 Crystal Structure of A Smad MH1 Domain Bound to DNA: Insights on DNA-binding in TGF-b Signaling.

论文摘要

Smad蛋白家族在癌症中常会发生肿瘤突变,它能将TGF-β信号从细胞膜介导到细胞核。在2.8 A分辨率下结合于最佳DNA序列的Smad3细胞MH1结构域的晶状结构揭示了一种新兴DNA结合基序。在晶状体中, 嵌入在DNA深沟中的保守性11个残基β结构专门提供了碱基特异性DNA识别。能被致瘤基因突变映射的某个表面环区已被确定为是很重要的Smad蛋白活性功能表面。此架构建立了了解在TGF-β应答基因的调控下Smad蛋白如何与其他转录因子发生协同作用框架。

Abstract

The Smad family of proteins, which are frequently targeted by tumorigenic mutations in cancer, mediate TGF-beta signaling from cell membrane to nucleus. The crystal structure of a Smad3 MH1 domain bound to an optimal DNA sequence determined at 2.8 A resolution reveals a novel DNA-binding motif. In the crystals, base-specific DNA recognition is provided exclusively by a conserved 11-residue beta hairpin that is embedded in the major groove of DNA. A surface loop region, to which tumorigenic mutations map, has been identified as a functional surface important for Smad activity. This structure establishes a framework for understanding how Smad proteins may act in concert with other transcription factors in the regulation of TGF-beta-responsive genes.

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