Our work suggests that the tryptophan cage motif plays a structural role, rather than in RNA recognition. An NMR structural ensemble of the hnRNPR-like protein DND1 eRRM1-RRM2 domains bound to RNA (PDB ID 7Q4L), solved by the Allain group, showed that this region does not contact RNA:

Finally, we compare to previously solved structures of hnRNPR-like proteins hnRNPRQ and DND1 to identify common features in the eRRM motif.

To see if these residues are biologically significant, we surveyed the COSMIC database and found several cancer-associated missense mutations in the tryptophan cage motif and residues in the Next-RRM interface:

Alanine substitution of residues in the Next-RRM interface or tryptophan cage reduce thermal stability and increase conformational dynamics, indicating an important role in protein folding: