A tale of two paralogs: human Transformer2 proteins with differential RNA-binding affinities.
|Title||A tale of two paralogs: human Transformer2 proteins with differential RNA-binding affinities.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Ghosh P, Grellscheid SNagaraja, Sowdhamini R|
|Journal||J Biomol Struct Dyn|
|Date Published||2015 Nov 26|
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 to 4000 virtual mutations were modelled on RNA and the domain-RNA interactions were studied after energy minimisation to convergence. Separately, another known 13-nucleotide stretch was docked and the domain-RNA interactions were 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.
|Alternate Journal||J. Biomol. Struct. Dyn.|