文章基本信息

标题：A binding motif for Siah ubiquitin ligase
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作者：Colin M. House ; Ian J. Frew ; Huei-Luen Huang 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：6
页码：3101-3106
DOI：10.1073/pnas.0534783100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The Drosophila SINA (seven in absentia) protein and its mammalian orthologs (Siah, seven in absentia homolog) are RING domain proteins that function in E3 ubiquitin ligase complexes and facilitate ubiquitination and degradation of a wide range of cellular proteins, including {beta}-catenin. Despite these diverse targets, the means by which SINA/Siah recognize substrates or binding proteins has remained unknown. Here we identify a peptide motif (RPVAxVxPxxR) that mediates the interaction of Siah protein with a range of protein partners. Sequence alignment and mutagenesis scanning revealed residues that are important to this interaction. This consensus sequence correctly predicted a high-affinity interaction with a peptide from the cytoskeletal protein plectin-1 (residues 95-117). The unusually high-affinity binding obtained with a 23-residue peptide (KDapp = 29 nM with SINA) suggests that it may serve as a useful dominant negative reagent for SINA/Siah proteins.