TY - DATA T1 - A Tale of Two Paralogs: Human Transformer2 proteins with differential RNA-binding affinities PY - 2015/09/26 AU - R. Sowdhamini AU - Pritha Ghosh AU - Sushma Nagaraja Grellscheid UR - https://tandf.figshare.com/articles/dataset/A_Tale_of_Two_Paralogs_Human_Transformer2_proteins_with_differential_RNA_binding_affinities/1568818 DO - 10.6084/m9.figshare.1568818.v1 L4 - https://ndownloader.figshare.com/files/2350867 L4 - https://ndownloader.figshare.com/files/2350869 L4 - https://ndownloader.figshare.com/files/3419054 L4 - https://ndownloader.figshare.com/files/3419060 L4 - https://ndownloader.figshare.com/files/2350875 L4 - https://ndownloader.figshare.com/files/3419066 L4 - https://ndownloader.figshare.com/files/2350879 L4 - https://ndownloader.figshare.com/files/2350881 L4 - https://ndownloader.figshare.com/files/2350883 L4 - https://ndownloader.figshare.com/files/2350885 L4 - https://ndownloader.figshare.com/files/2350887 L4 - https://ndownloader.figshare.com/files/2350889 L4 - https://ndownloader.figshare.com/files/2350891 L4 - https://ndownloader.figshare.com/files/2350893 L4 - https://ndownloader.figshare.com/files/3419075 L4 - https://ndownloader.figshare.com/files/2350897 L4 - https://ndownloader.figshare.com/files/3419084 L4 - https://ndownloader.figshare.com/files/3419087 KW - transformer 2 KW - dynamics studies KW - energy minimization KW - solution structure KW - rna KW - binding specificities KW - Human Transformer 2 proteins KW - backup circuit KW - paralog compensation KW - proteins display KW - Drosophila Tra 2 protein N2 - The Transformer2 (Tra2) proteins in humans are homologues of the Drosophila Tra2 protein. One of the two RNA-binding paralogs, Tra2β, has been very well-studied over the past decade, but not much is known about Tra2α. It was very recently shown that the two proteins demonstrate the phenomenon of paralog compensation. Here, we provide a structural basis for this genetic backup circuit, using molecular modelling and dynamics studies. We show that the two proteins display similar binding specificities, but differential affinities to a short GAA-rich RNA stretch. Starting from the 6-nucleotide RNA in the solution structure, close to4000 virtual mutations were modelled on RNA and the domain-RNA interactionswere studied after energy minimization to convergence. Separately, anotherknown 13-nucleotide stretch was docked and the domain-RNA interactionswere observed through a 100-ns dynamics trajectory. We have also demonstrated the ‘compensatory’ mechanism at the level of domains in one of the domain repeat-containing RNA-binding proteins. ER -