The structural basis for molecular recognition by the vitamin B 12 RNA aptamer

Area of Science:

• Structural Biology
• Molecular Biology
• Biochemistry

Background:

• Ligand-binding RNA aptamers typically recognize targets through coupled folding and binding.
• Previous structural studies indicate RNA folds around ligands, integrating folding and binding processes.

Purpose of the Study:

• To elucidate the molecular recognition mechanism of the cyanocobalamin (vitamin B12) aptamer.
• To determine the 3 Å crystal structure of the vitamin B12 aptamer.

Main Methods:

• X-ray crystallography at 3 Å resolution.
• Structural analysis of RNA-ligand interactions.

Main Results:

• A novel RNA structure for vitamin B12 recognition was determined.
• The structure features a locally folding RNA triplex stabilized by a three-stranded zipper.
• A duplex stacked on the triplex forms a cleft, creating the vitamin B12 binding site.
• Interactions include hydrophobic packing, hydrogen bonding, and dipolar forces.

Conclusions:

• The vitamin B12 aptamer employs a distinct molecular recognition strategy compared to other RNA aptamers.
• This mechanism involves pre-formed secondary structures forming a docking surface for the ligand.
• The findings suggest potential uncoupling of RNA folding and binding, similar to protein-ligand complexes.