Blue boxes indicate the P5a and P5c arms involved in binding to Fab2. Brown corresponds to protections arising from the ΔC209 P4-P6 tertiary structure blue corresponds to additional protections induced by Fab2 binding. Nucleotides in color within the secondary structure represent residues protected from hydroxyl radicals. Residue numbering (102–261) corresponds to the Tetrahymena group I intron. ( A) ΔC209 P4-P6 primary and secondary structure schematic. The RNA antigen: ΔC209 P4-P6 independently folding domain derived from Tetrahymena group I intron. These findings yield valuable insights for engineering of Fabs as RNA-binding modules and facilitate further development of Fabs as possible therapeutic drugs and biochemical tools to explore RNA biology. The Fab-RNA interface also differs significantly from Fab-protein interfaces in amino acid composition and light-chain participation. The crystal structure reveals that the Fab achieves specific RNA binding on a shallow surface with complementarity-determining region (CDR) sequence diversity, length variability, and main-chain conformational plasticity. Capability in phasing and crystal contact formation suggests that the Fab provides a potentially valuable crystal chaperone for RNA.

We have solved the crystal structure of the first Fab-RNA complex at 1.95 A. Here we have developed a robust approach using a synthetic phage-display library to select specific antigen-binding fragments (Fabs) targeting a large functional RNA. However, knowledge of RNA-binding antibodies and their application in the ever-growing RNA field is lacking. Antibodies that bind protein antigens are indispensable in biochemical research and modern medicine.

Jing dong ye