Role of dimerization in KH/RNA complexes: the example of Nova KH3

Biochemistry
Andres RamosAnnalisa Pastore

Abstract

The K homology module, one of the most common RNA-binding motifs, is present in multiple copies in both prokaryotic and eukaryotic regulatory proteins. Increasing evidence suggests that self-aggregation of KH modules has a functional role. We have used a combination of techniques to characterize the behavior in solution of the third KH domain of Nova-1, a paradigmatic KH protein. The possibility of working on the isolated module allowed us to observe specifically the homodimerization and RNA-binding properties of KH domains. We provide conclusive evidence that self-association of Nova-1 KH3 occurs in solution even in the absence of RNA. Homodimerization involves a specific protein/protein interface. We also studied the dynamical behavior of Nova-1 KH3 in isolation and in complex with RNA. These data provide a model for the mechanism of KH/RNA recognition and suggest functional implications of dimerization in KH complexes. We discuss our findings in the context of the whole KH family and suggest a generalized mode of interaction.

References

Nov 1, 1992·Journal of Biomolecular NMR·M PiottoV Sklenár
Jul 14, 1995·Journal of Molecular Biology·F H Allain, G Varani
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Feb 17, 2001·Current Opinion in Structural Biology·J M Pérez-Cañadillas, G Varani
Jul 1, 1995·Journal of Biomolecular NMR·C BartelsK Wüthrich

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Citations

Apr 8, 2011·European Biophysics Journal : EBJ·Cyprian D Cukier, Andres Ramos
May 3, 2007·Nature Reviews. Molecular Cell Biology·Bradley M LundeGabriele Varani
Feb 10, 2009·Nature Structural & Molecular Biology·Irene Díaz-MorenoAndres Ramos
Jul 30, 2010·Molecular Biology of the Cell·Congli CaiKathleen Molyneaux
May 2, 2012·Nucleic Acids Research·David HollingworthAndres Ramos
Jan 14, 2016·Nature Communications·Mikael FeracciCyril Dominguez
Apr 22, 2008·The FEBS Journal·Roberto ValverdeLynne Regan
Mar 18, 2006·Biochemical and Biophysical Research Communications·C-P Benny YiuH Y Edwin Chan
Mar 13, 2010·Structure·Cyprian D Cukier, Andres Ramos
Jan 1, 2017·Plant Biology·M MuthuramalingamR Mahalingam
Jan 14, 2004·Nature Structural & Molecular Biology·Sean P RyderJames R Williamson
Jul 28, 2007·Journal of the American Chemical Society·Barbara BeuthAndres Ramos

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