Methyl dynamics for understanding hydrophobic core packing of dynamically different motifs of double-stranded RNA binding domain of protein kinase R.
Double-stranded RNA binding domains of human protein kinase R (dsRBD-PKR) regulate distinct cellular functions and the fate of an RNA molecule in the cell. This highly homologous domains present in multiple copies in a number of species, exhibit individual and specific functional specificity. Number of NMR and X-ray crystallographic structural studies reveals that such domains take a common alpha-beta-beta-beta-alpha tertiary fold. However, the functional specificities of these domains could be due to the dynamics of the individual amino acid residues, as has been shown earlier in the case of backbone dynamics of 15N-1H of dsRNA binding motifs (dsRBMs) of human protein kinase R (PKR) (Nanduri S, Rahman F, Williams BRG, Qin J. EMBO J 2000;19:5567-5574). To further investigate if the differences in dynamics of the two dsRBMs are restricted to only backbone, or if the side-chain motions are also different to the extent of influencing their packing of the two hydrophobic cores, we have investigated the methyl group dynamics using 13C-methyl relaxation measurements. The results show that the hydrophobic core of dsRBM1 is more tightly packed than dsRBM2, and it seems to undergo less fast scale motions in the subnanosecond regime.
Barnwal
Ravi P
RP
Department of Chemical Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai, India. barnwal@tifr.res.in
Chaudhuri
Tista R
TR
Nanduri
S
S
Qin
J
J
Chary
K V R
KV
D019943:Amino Acid Substitution; D001665:Binding Sites; D007700:Kinetics; D008745:Methylation; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D012330:RNA, Double-Stranded / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D019892:eIF-2 Kinase / Q000737:chemistry* / Q000378:metabolism*
D012330:RNA, Double-Stranded; D011994:Recombinant Proteins; D019892:eIF-2 Kinase