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.
Biophysics Laboratories, Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, St. Michael's Building, Portsmouth PO1 2DT, UK.
Caterina
C
Alfano
Domenico
D
Sanfelice
Jeff
J
Babon
Geoff
G
Kelly
Amanda
A
Jacks
Stephen
S
Curry
Maria R
MR
Conte
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