Section 23.2.4.5. Stem loops

One fascinating observation in viewing the structures of RNA-binding proteins, even in the absence of RNA, is that aside from the tRNA-binding synthetases, they all appear to have evolved from or towards a very similar general fold (Burd & Dreyfuss, 1994). This fold, exemplified by the RNP domain found in numerous RNA-binding proteins, consists of a β-sheet surrounded on one side by α-helices and solvent-exposed on the opposing face. This general folding architecture is found in RNP domains, ribosome proteins, K-homologous domains (KH), double-stranded RNA-binding domains and cold shock proteins. Although each of these subsets of RNA-binding domains has a different topology and most probably bind to RNA with different surfaces, they all appear to have this alpha–beta–solvent architecture.

Two proteins with this architecture have been co-crystallized with their specific RNA stem-loop ligands (Nagai et al., 1995; van den Worm et al., 1998). In both cases, the loop of the RNA binds to the open face of the β-sheet where solvent-exposed aromatic amino-acid side chains stack with the extrahelical bases of the RNA. Unpaired bases from the RNA also form numerous specific hydrogen bonds with protein side chains and polar backbone groups, imparting sequence specificity in the interaction. These structures suggest that the flat, open face of a β-sheet provides a good surface for RNA binding, where the extrahelical bases can make extensive and specific contacts with the protein.