Gonzalez Grecia M, Hardwick Steven W, Maslen Sarah L, Skehel J Mark, Holmqvist Erik, Vogel Jörg, Bateman Alex, Luisi Ben F, Broadhurst R William
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
RNA. 2017 May;23(5):696-711. doi: 10.1261/rna.060343.116. Epub 2017 Feb 13.
The protein ProQ has recently been identified as a global small noncoding RNA-binding protein in , and a similar role is anticipated for its numerous homologs in divergent bacterial species. We report the solution structure of ProQ, revealing an N-terminal FinO-like domain, a C-terminal domain that unexpectedly has a Tudor domain fold commonly found in eukaryotes, and an elongated bridging intradomain linker that is flexible but nonetheless incompressible. Structure-based sequence analysis suggests that the Tudor domain was acquired through horizontal gene transfer and gene fusion to the ancestral FinO-like domain. Through a combination of biochemical and biophysical approaches, we have mapped putative RNA-binding surfaces on all three domains of ProQ and modeled the protein's conformation in the and RNA-bound forms. Taken together, these data suggest how the FinO, Tudor, and linker domains of ProQ cooperate to recognize complex RNA structures and serve to promote RNA-mediated regulation.
蛋白质ProQ最近被鉴定为一种全局性小非编码RNA结合蛋白，并且预计其在不同细菌物种中的众多同源物也具有类似作用。我们报道了ProQ的溶液结构，揭示了一个N端FinO样结构域、一个C端结构域（意外地具有真核生物中常见的Tudor结构域折叠）以及一个细长的桥接结构域内连接子，该连接子具有柔性但不可压缩。基于结构的序列分析表明，Tudor结构域是通过水平基因转移和基因融合到祖先FinO样结构域而获得的。通过生化和生物物理方法相结合，我们在ProQ的所有三个结构域上绘制了假定的RNA结合表面，并对该蛋白在游离和RNA结合形式下的构象进行了建模。综合这些数据，表明了ProQ的FinO、Tudor和连接子结构域如何协同识别复杂的RNA结构并促进RNA介导的调控。
