Structural analysis of cooperative RNA binding by the La motif and central RRM domain of human La protein.
The La protein is a conserved component of eukaryotic ribonucleoprotein complexes that binds the 3' poly(U)-rich elements of nascent RNA polymerase III (pol III) transcripts to assist folding and maturation. This specific recognition is mediated by the N-terminal domain (NTD) of La, which comprises a La motif and an RNA recognition motif (RRM). We have determined the solution structures of both domains and show that the La motif adopts an alpha/beta fold that comprises a winged-helix motif elaborated by the insertion of three helices. Chemical shift mapping experiments show that these insertions are involved in RNA interactions. They further delineate a distinct surface patch on each domain-containing both basic and aromatic residues-that interacts with RNA and accounts for the cooperative binding of short oligonucleotides exhibited by the La NTD.
Alfano
Caterina
C
Biophysics Laboratories, Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, St. Michael's Building, Portsmouth PO1 2DT, UK.
Sanfelice
Domenico
D
Babon
Jeff
J
Kelly
Geoff
G
Jacks
Amanda
A
Curry
Stephen
S
Conte
Maria R
MR
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens; D001665:Binding Sites; D017124:Conserved Sequence; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000097585:SS-B Antigen
D001324:Autoantigens; D012313:RNA; D012261:Ribonucleoproteins; D000097585:SS-B Antigen