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BRCT(BRCA1C-terminus)是真核生物DNA损伤修复系统重要的信号传导和蛋白靶向结构域。为了探讨含磷酸结合口袋的BRCT与磷酸化配体结合的机制,对XRCC1BRCT1、PTIP BRCT4、ECT2BRCT1和TopBP1BRCT1进行了结构保守性和表面静电势分析。结果显示,4个BRCT的磷酸结合口袋周围所存在的结构保守并带正电势的沟槽很可能是其功能位点,并且类似的沟槽在含磷酸结合口袋的BRCT中普遍存在。沟槽两侧及底部均带有极性氨基酸残基,两侧带正电荷,而底部疏水。这说明沟槽与配体的结合以静电和疏水相互作用为主。沟槽主要位于单个BRCT中,而且4个BRCT的沟槽在形状和电荷分布上都不同,说确明BRCT配体特异性主要由单个BRCT决定。磷酸结合口袋位于沟槽中心,说明沟槽可能同时结合磷酸化残基的N端和C端附近残基。
BRCT (BRCA1C-terminus) is an important signal transduction and protein targeting domain of eukaryotic DNA damage repair system. In order to investigate the mechanism of binding between BRCT and phosphorylated ligand in phosphate-binding pocket, structural conservation and surface electrostatic potential analysis of XRCC1BRCT1, PTIP BRCT4, ECT2BRCT1 and TopBP1BRCT1 were performed. The results show that the structurally conserved and positively charged trenches present around the phosphate binding pocket of the four BRCTs are likely to be functional sites and that similar trenches are prevalent in BRCTs containing phosphate-binding pockets. Polar amino acid residues are present on both sides and at the bottom of the trench, with positive charges on both sides and hydrophobic bottom. This shows that the combination of trenches and ligands is dominated by electrostatic and hydrophobic interaction. The trenches are mainly located in a single BRCT, and the grooves of the four BRCTs are different in shape and charge distribution, confirming that the specificity of the BRCT ligand is mainly determined by a single BRCT. The phosphate binding pocket is located in the center of the groove, indicating that the groove may bind both N-terminal and C-terminal residues of the phosphorylated residues simultaneously.