Molecular basis of double-stranded RNA-protein interactions: structure of a dsRNA-binding domain complexed with dsRNA.
Protein interactions with double-stranded RNA (dsRNA) are critical for many cell processes; however, in contrast to protein-dsDNA interactions, surprisingly little is known about the molecular basis of protein-dsRNA interactions. A large and diverse class of proteins that bind dsRNA do so by utilizing an approximately 70 amino acid motif referred to as the dsRNA-binding domain (dsRBD). We have determined a 1.9 A resolution crystal structure of the second dsRBD of Xenopus laevis RNA-binding protein A complexed with dsRNA. The structure shows that the protein spans 16 bp of dsRNA, interacting with two successive minor grooves and across the intervening major groove on one face of a primarily A-form RNA helix. The nature of these interactions explains dsRBD specificity for dsRNA (over ssRNA or dsDNA) and the apparent lack of sequence specificity. Interestingly, the dsRBD fold resembles a portion of the conserved core structure of a family of polynucleotidyl transferases that includes RuvC, MuA transposase, retroviral integrase and RNase H. Structural comparisons of the dsRBD-dsRNA complex and models proposed for polynucleotidyl transferase-nucleic acid complexes suggest that similarities in nucleic acid binding also exist between these families of proteins.
Ryter
J M
JM
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA.
Schultz
S C
SC
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016384:Consensus Sequence; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009713:Nucleotidyltransferases / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D012330:RNA, Double-Stranded / Q000737:chemistry*; D016601:RNA-Binding Proteins / Q000737:chemistry*; D029867:Xenopus Proteins; D014982:Xenopus laevis
D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; D029867:Xenopus Proteins; C107296:Xlrbpa protein, Xenopus; D009713:Nucleotidyltransferases