• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Solvent Exposed Non-contacting Amino Acids Play a Critical Role in NF-kappaB/IkappaBalpha Complex Formation.
【24h】

Solvent Exposed Non-contacting Amino Acids Play a Critical Role in NF-kappaB/IkappaBalpha Complex Formation.

机译：溶剂暴露的非接触氨基酸在NF-κB/ IkappaBalpha复合物的形成中起关键作用。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

IkappaBalpha inhibits transcription factor NF-kappaB activity by specific binding to NF-kappaB heterodimers composed of p65 and p50 subunits. It binds with slightly lower affinity to p65 homodimers and with significantly lower affinity to homodimers of p50. We have employed a structure-based mutagenesis approach coupled with protein-protein interaction assays to determine the source of this dimer selectivity exhibited by IkappaBalpha. Mutation of amino acid residues in IkappaBalpha that contact NF-kappaB only marginally affects complex binding affinity, indicating a lack of hot spots in NF-kappaB/IkappaBalpha complex formation. Conversion of the weak binding NF-kappaB p50 homodimer into a high affinity binding partner of IkappaBalpha requires transfer of both the NLS polypeptide and amino acid residues Asn202 and Ser203 from the NF-kappaB p65 subunit. Involvement of Asn202 and Ser203 in complex formation is surprising as these amino acid residues occupy solvent exposed positions at a distance of 20A from IkappaBalpha in the crystal structures. However, the same amino acid residue positions have been genetically isolated as determinants of binding specificity in a homologous system in Drosophila. X-ray crystallographic and solvent accessibility experiments suggest that these solvent-exposed amino acid residues contribute to NF-kappaB/IkappaBalpha complex formation by modulating the NF-kappaB p65 subunit NLS polypeptide.
机译：IkappaBalpha通过与由p65和p50亚基组成的NF-kappaB异二聚体特异性结合，抑制转录因子NF-kappaB的活性。它与p65同二聚体的亲和力略低，而与p50同二聚体的亲和力则低得多。我们采用了一种基于结构的诱变方法，结合蛋白质-蛋白质相互作用测定法来确定由IkappaBalpha表现出的这种二聚体选择性的来源。 IkappaBalpha中与NF-kappaB接触的氨基酸残基突变仅轻微影响复合物结合亲和力，表明NF-kappaB / IkappaBalpha复合物形成中缺乏热点。将弱结合的NF-kappaB p50同二聚体转化为IkappaBalpha的高亲和力结合伴侣，需要同时从NF-kappaB p65亚基转移NLS多肽以及氨基酸残基Asn202和Ser203。 Asn202和Ser203参与复合物形成是令人惊讶的，因为这些氨基酸残基在晶体结构中与IkappaBalpha相距20A的位置占据了溶剂暴露的位置。但是，已经通过遗传分离了相同的氨基酸残基位置，作为果蝇同源系统中结合特异性的决定因素。 X射线晶体学和溶剂可及性实验表明，这些溶剂暴露的氨基酸残基通过调节NF-κBp65亚基NLS多肽而有助于NF-κB/IκBα复合物的形成。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号