Pritha Ghosh
A tale of two paralogs: human Transformer2 proteins with differential RNA-binding affinities
Ghosh, Pritha; Grellscheid, Sushma Nagaraja; Sowdhamini, R.
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.
Citation
Ghosh, P., Grellscheid, S. N., & Sowdhamini, R. (2016). A tale of two paralogs: human Transformer2 proteins with differential RNA-binding affinities. Journal of Biomolecular Structure and Dynamics, 34(9), 1979-1986. https://doi.org/10.1080/07391102.2015.1100551
Journal Article Type | Article |
---|---|
Acceptance Date | Sep 15, 2015 |
Online Publication Date | Nov 26, 2015 |
Publication Date | 2016-09 |
Deposit Date | Aug 25, 2017 |
Journal | Journal of Biomolecular Structure and Dynamics |
Print ISSN | 0739-1102 |
Electronic ISSN | 1538-0254 |
Publisher | Taylor and Francis Group |
Peer Reviewed | Peer Reviewed |
Volume | 34 |
Issue | 9 |
Pages | 1979-1986 |
DOI | https://doi.org/10.1080/07391102.2015.1100551 |
Public URL | https://durham-repository.worktribe.com/output/1377985 |
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