Urea Dependent (15)N NMR-Relaxation Studies on PfP2 Multimers Reveal that the C-Terminal Behaves like an Independent Intrinsically Disordered Peptide.

Abstract

Intrinsically disordered proteins or such domains in globular proteins are believed to be playing important roles in protein functions by virtue of their ability to adapt themselves to requirements of different binding partners and thereby accord high specificity to the interaction. Eukaryotic ribosomal stalk is made up of a supramolecular assembly of P0, P1 and P2 proteins. In Plasmodium falciparum, homo-oligomers of P2 are also seen which seem to be involved in many non-ribosomal functions of the protein in the parasite, and in all of these the protein interacts with different interactors. Here we show by extensive (15)N NMR relaxation studies that the C-terminal stretch of about 45 residues of the protein always remains as a flexible disordered domain, regardless of the state of association of the protein. The relaxation behaviors and the derived rotational correlation times for this portion of the protein are essentially the same in the presence of different concentrations of urea which produce different mixtures of PfP2 oligomers in rapid exchange, whereas the rest of the protein shows substantial variations with urea concentration in the relaxation behaviors. In other words, the C-terminal domain behaves as if it were an independent intrinsically disordered peptide. This would augment the notion that the C-terminal domain of PfP2 would be acting as a scavenger for different interactors depending upon the different functions of the protein inside the parasite.