Crystal Structure of a Variant PAM2 Motif of LARP4B Bound to the MLLE Domain of PABPC1
Crystal Structure of a Variant PAM2 Motif of LARP4B Bound to the MLLE Domain of PABPC1
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DOI：
10.3390/biom10060872
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发表时间：
2020-06-01
期刊：
影响因子：
5.5
通讯作者：
Fischer, Utz
中科院分区：
文献类型：
--
作者：
Grimm, Clemens;Pelz, Jann-Patrick;Fischer, Utz
真核细胞通过调节mRNA转录、定位、翻译和周转率来决定其遗传程序的蛋白质输出。这种调节是通过一系列RNA结合蛋白（RBP）来实现的，这些蛋白结合任何给定的mRNA，从而形成mRNP。多聚腺苷酸结合蛋白（PABP）是几乎所有具有多聚腺苷酸尾的mRNP的重要成员。它们作为多功能支架，允许将含有多聚（A）相互作用基序（PAM）的多种因子募集到mRNP中。我们目前的晶体结构的变体PAM基序（称为PAM 2 w）的N-末端部分的正翻译因子LARP 4 B，它结合的MLLE结构域的聚（A）结合蛋白C1胞质1（PABPC 1）。结构分析，沿着体外和体内的突变研究，揭示了PAM 2基序和MLLE结构域之间相互作用的新模式。
Eukaryotic cells determine the protein output of their genetic program by regulating mRNA transcription, localization, translation and turnover rates. This regulation is accomplished by an ensemble of RNA-binding proteins (RBPs) that bind to any given mRNA, thus forming mRNPs. Poly(A) binding proteins (PABPs) are prominent members of virtually all mRNPs that possess poly(A) tails. They serve as multifunctional scaffolds, allowing the recruitment of diverse factors containing a poly(A)-interacting motif (PAM) into mRNPs. We present the crystal structure of the variant PAM motif (termed PAM2w) in the N-terminal part of the positive translation factor LARP4B, which binds to the MLLE domain of the poly(A) binding protein C1 cytoplasmic 1 (PABPC1). The structural analysis, along with mutational studies in vitro and in vivo, uncovered a new mode of interaction between PAM2 motifs and MLLE domains.