Morozova N, Allers J, Myers J, Shamoo Y
Department of Biochemistry and Cell Biology, Rice University 6100 Main Street, Houston, TX 77005, USA.
Bioinformatics. 2006 Nov 15;22(22):2746-52. doi: 10.1093/bioinformatics/btl470. Epub 2006 Sep 11.
The recognition of specific RNA sequences and structures by proteins is critical to our understanding of RNA processing, gene expression and viral replication. The diversity of RNA structures suggests that RNA recognition is substantially different than that of DNA.
The atomic coordinates of 41 protein-RNA complexes have been used to probe composite nucleoside binding pockets that form the structural and chemical underpinnings of base recognition. Composite nucleoside binding pockets were constructed using three-dimensional superpositions of each RNA nucleoside. Unlike protein-DNA interactions which are dominated by accessibility, RNA recognition frequently occurs in non-canonical and single-strand-like structures that allow interactions to occur from a much wider set of geometries and make fuller use of unique base shapes and hydrogen-bonding ability. By constructing composites that include all van der Waals, hydrogen-bonding, stacking and general non-polar interactions made to a particular nucleoside, the strategies employed are made readily visible. Protein-RNA interactions can result in the formation of a glove-like tight binding pocket around RNA bases, but the size, shape and non-polar binding patterns differ between specific RNA bases. We show that adenine can be distinguished from guanine based on the size and shape of the binding pocket and steric exclusion of the guanine N2 exocyclic amino group. The unique shape and hydrogen-bonding pattern for each RNA base allow proteins to make specific interactions through a very small number of contacts, as few as two in some cases.
The program ENTANGLE is available from http://www.bioc.rice.edu/~shamoo
蛋白质对特定RNA序列和结构的识别对于我们理解RNA加工、基因表达和病毒复制至关重要。RNA结构的多样性表明RNA识别与DNA识别有很大不同。
41个蛋白质-RNA复合物的原子坐标已被用于探测复合核苷结合口袋，这些口袋构成了碱基识别的结构和化学基础。复合核苷结合口袋是通过对每个RNA核苷进行三维叠加构建的。与以可及性为主导的蛋白质-DNA相互作用不同，RNA识别经常发生在非经典和单链状结构中，这种结构允许从更广泛的几何构型进行相互作用，并更充分地利用独特的碱基形状和氢键结合能力。通过构建包含与特定核苷发生的所有范德华力、氢键、堆积和一般非极性相互作用的复合物，所采用的策略变得清晰可见。蛋白质-RNA相互作用可导致在RNA碱基周围形成手套状紧密结合口袋，但特定RNA碱基之间的大小、形状和非极性结合模式有所不同。我们表明，基于结合口袋的大小和形状以及鸟嘌呤N2外环氨基的空间排斥作用，可以将腺嘌呤与鸟嘌呤区分开来。每个RNA碱基独特的形状和氢键模式使蛋白质能够通过极少数接触（在某些情况下少至两个）进行特异性相互作用。
程序ENTANGLE可从http://www.bioc.rice.edu/~shamoo获得
