Department of Biochemistry and Groupe de Recherche axé sur la Structure des Protéines, McGill University, Montréal, Québec H3G1Y6, Canada.
J Biol Chem. 2010 Apr 30;285(18):13599-606. doi: 10.1074/jbc.M109.089540. Epub 2010 Feb 24.
Poly(A)-binding protein (PABPC1) is involved in multiple aspects of mRNA processing and translation. It is a component of RNA stress granules and binds the RNA-induced silencing complex to promote degradation of silenced mRNAs. Here, we report the crystal structures of the C-terminal Mlle (or PABC) domain in complex with peptides from GW182 (TNRC6C) and Ataxin-2. The structures reveal overlapping binding sites but with unexpected diversity in the peptide conformation and residues involved in binding. The mutagenesis and binding studies show low to submicromolar binding affinity with overlapping but distinct specificity determinants. These results rationalize the role of the Mlle domain of PABPC1 in microRNA-mediated mRNA deadenylation and suggest a more general function in the assembly of cytoplasmic RNA granules.
多聚（A）结合蛋白（PABPC1）参与 mRNA 处理和翻译的多个方面。它是 RNA 应激颗粒的组成部分，与 RNA 诱导的沉默复合物结合，促进沉默 mRNAs 的降解。在这里，我们报告了与 GW182（TNRC6C）和 Ataxin-2 肽复合物的 C 端 Mlle（或 PABC）结构域的晶体结构。这些结构揭示了重叠的结合位点，但肽构象和参与结合的残基存在出乎意料的多样性。突变和结合研究表明，与重叠但独特的特异性决定因素结合的亲和力低至亚毫摩尔。这些结果合理地解释了 PABPC1 的 Mlle 结构域在 microRNA 介导的 mRNA 去腺苷酸化中的作用，并暗示了其在细胞质 RNA 颗粒组装中的更普遍功能。
