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J Biomol Struct Dyn. 2016 Sep;34(9):1979-86. doi: 10.1080/07391102.2015.1100551. Epub 2015 Nov 26.

A tale of two paralogs: human Transformer2 proteins with differential RNA-binding affinities.

Author information

1
a National Centre for Biological Sciences , Tata Institute of Fundamental Research , GKVK Campus, Bellary Road, Bangalore 560065 , Karnataka , India.
2
b School of Biological and Biomedical Sciences , Durham University , Durham , UK.

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.

KEYWORDS:

Protein–RNA binding; TRA2 protein; ligand affinity; molecular dynamics; molecular modelling

PMID:
26414300
DOI:
10.1080/07391102.2015.1100551
[Indexed for MEDLINE]

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