Structural basis of ligand discrimination by two related RNA aptamers resolved by NMR spectroscopy.
In a previous study, an RNA aptamer for the specific recognition of arginine was evolved from a parent sequence that bound citrulline specifically. The two RNAs differ at only 3 positions out of 44. The solution structures of the two aptamers complexed to their cognate amino acids have now been determined by two-dimensional nuclear magnetic resonance spectroscopy. Both aptamers contain two asymmetrical internal loops that are not well ordered in the free RNA but that fold into a compact structure upon ligand binding. Those nucleotides common to both RNAs include a conserved cluster of purine residues, three of which form an uneven plane containing a G:G pair, and two other residues nearly perpendicular to that surface. Two of the three variant nucleotides are stacked on the cluster of purines and form a triple contact to the amino acid side chain, whereas the edge of the third variant nucleotide is capping the binding pocket.
Yang
Y
Y
Centre de Biochimie Structurale (CBS), Unité Mixte de Recherche, CNRS 9955, Montpellier, France.
Kochoyan
M
M
Burgstaller
P
P
Westhof
E
E
Famulok
M
M
D001120:Arginine / Q000737:chemistry / Q000378:metabolism*; D001482:Base Composition; D001483:Base Sequence; D002956:Citrulline / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D008024:Ligands; D002956:Citrulline; D012313:RNA; D001120:Arginine