A-form DNA (Figure 10.1a). These duplexes may be recognized more by shape and groove width than by
specific hydrogen-bonding contacts. An example from the bacterial ribosome shows how a -strand lies
in the groove of a duplex RNA, while the bases in a single-stranded region are contacted by an -helical
region of the protein (Figure 10.3b). The intricate three-dimensional folds of RNA add to its ability to
make an induced fit in recognition of protein, for example, during the charging of transfer RNA with
amino acids by tRNA synthetases (Sections 7.3.2 and 10.9.3).
10.2 The Physical Chemistry of Protein–Nucleic Acid Interactions
Since the 1990s, many hundreds of crystal and NMR structures have been solved for protein–DNA and
protein–RNA complexes. These structures illustrate the diversity of nucleic acid–protein recognition pat-
terns. To understand such complicated molecular architectures, we need to explore the forces that hold the
components together.
10.2.1 Hydrogen Bonding Interactions
Although energetically rather weak, hydrogen bonding interactionsare a key component of protein–nucleic
acid recognition, since collectively they confer sequence-specificity in the majority of cases. In solution, all
exposed polar groups form hydrogen bonds with water molecules. When the solvent is removed from these
groups, as happens in the formation of a protein/nucleic acid complex, they must make compensating inter-
actions with other polar groups. The energy of the hydrogen-bonding interaction is optimal when the atoms
of the donorand acceptorgroups (X, H and Y) and the lone electron pair are all arranged linearly, as indi-
cated in the scheme
XHYRProtein–Nucleic Acid Interactions 387
Figure 10.3 Representative complexes of protein with RNA. (a) An RNA hairpin, in complex with the RNP protein
U1 from the eukaryotic intron-splicing machinery (PDB: 1URN). The bases of the single-stranded loop
are recognized by contacts with the protein side chains. (b) A view of a section of the ribosome, show-
ing an even more complicated RNA/protein interaction (PDB: 1IBM). A b-strand lies in the groove of the
duplex RNA and the bases in a single-stranded region are contacted by an a-helical region