Interaction analysis of the AAA+ domain of the heterochromatin protein Sir3

异染色质蛋白 Sir3 AAA 结构域的相互作用分析

• 批准号: 218553752
• 负责人: Professorin Dr. Ann Elizabeth Ehrenhofer-Murray
• 金额: --
• 依托单位: Arbeitsgruppe Molekulare Zellbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/218553752?language=en
• 关键词: Interaction; analysis; AAA+; domain; heterochromatin

The silent information regulator 2/3/4 (SIR) complex is an archetypal heterochromatin complex re-quired for gene silencing at the silent mating-type loci and the telomeres in the yeast Saccharomyces cerevisiae. The Sir3 component consists of an N-terminal bromo-adjacent homology (BAH) domain and a C-terminal AAA+ ATPase-like domain. In a recent study, we have determined the crystal struc-ture of the AAA+ domain and, through an exhaustive mutational analysis, have identified several sur-face regions on this domain required for Sir3 silencing function, one of which we have shown repre-sents a site of interaction with Sir4. Based on these results, we here will determine the interaction partners of three other surface domains using a combination of genetics, molecular biology and bio-chemistry. Furthermore, we will define the region on Sir4 that interacts with Sir3. This detailed molecu-lar information about protein interactions within the SIR complex and with chromatin will be comple-mentary to structural information on the SIR complex and will for the first time provide molecular in-sight into a heterochromatin complex.

沉默信息调节因子2/3/4 （SIR）复合体是酵母沉默交配型位点和端粒基因沉默所需的典型异染色质复合体。Sir3组分由n端溴邻同源（BAH）结构域和c端AAA+ atp样结构域组成。在最近的一项研究中，我们确定了AAA+结构域的晶体结构，并通过详尽的突变分析，确定了该结构域上Sir3沉默功能所需的几个表面区域，其中一个我们已经证明代表了与Sir4相互作用的位点。基于这些结果，我们将结合遗传学、分子生物学和生物化学来确定其他三个表面结构域的相互作用伙伴。此外，我们将定义Sir4上与Sir3相互作用的区域。这些关于SIR复合体内部蛋白质相互作用以及与染色质相互作用的详细分子信息将是对SIR复合体结构信息的补充，并将首次为异染色质复合体提供分子视角。

项目成果

Architektur eines Heterochromatinkomplexes

异染色质复合体的结构

• DOI: 10.1007/s12268-015-0618-3
• 发表时间: 2015
• 期刊: BIOspektrum
• 作者: Ann Ehrenhofer-Murray