Formation of an amino-acid-binding pocket through adaptive zippering-up of a large DNA hairpin loop.
BACKGROUND
In vitro selection has identified DNA aptamers that target cofactors, amino acids, peptides and proteins. Structure determination of such ligand-DNA aptamer complexes should elucidate the details of adaptive DNA structural transitions, binding-pocket architectures and ligand recognition. We have determined the solution structure of the complex of a DNA aptamer containing a guanine-rich 18-residue hairpin loop that binds L-argininamide with approximately 100 microM affinity.


RESULTS
The DNA aptamer generates its L-argininamide-binding pocket by adaptive zippering up the 18-residue loop through formation of Watson-Crick pairs, mismatch pairs and base triples, while maximizing stacking interactions. Three of the four base triples involve minor-groove recognition through sheared G.A mismatch formation. The unique fold is also achieved through positioning of an adenine residue deep within the minor groove and through nestling of a smaller loop within the larger loop on complex formation. The accessibility to the unique L-argininamide-binding pocket is restricted by a base pair that bridges across one side of the major-groove-binding site. The guanidinium group of the bound L-argininamide aligns through intermolecular hydrogen-bond formation with the base edges of nonadjacent guanine and cytosine residues while being sandwiched between the planes of nonadjacent guanine residues.


CONCLUSIONS
The available structures of L-arginine/L-argininamide bound to their DNA and RNA targets define the common principles and patterns associated with molecular recognition, as well as the diversity of intermolecular hydrogen-bonding alignments associated with the distinct binding pockets.
Lin
C H
CH
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Wang
W
W
Jones
R A
RA
Patel
D J
DJ
D000596:Amino Acids / Q000378:metabolism*; D020137:Base Pair Mismatch; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009587:Nitrogen Isotopes; D009690:Nucleic Acid Conformation; D011485:Protein Binding
D000596:Amino Acids; D009587:Nitrogen Isotopes; D004247:DNA