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 |
Volume | 34 |
Issue | 9 |
Start Page | 1979 |
Pagination | 1979-86 |
Date Published | 2015 Nov 26 |
ISSN | 1538-0254 |
Abstract | 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. |
DOI | 10.1080/07391102.2015.1100551 |
Alternate Journal | J. Biomol. Struct. Dyn. |
PubMed ID | 26414300 |