occurring oligonucleotide/oligosaccaride-binding fold(the OB fold). This structure has an anti-parallel
-barrel, and it has an overall shape like the capstan of a ship, with part of the concave surface used to
engage the single-stranded DNA. Comparison of the OB folds for several different proteins (Pot1, the
telomere end-binding protein (TEBP) from the ciliated protozoan Oxytricha nova, and the human replica-
tion protein A) illustrates how the common core of all three proteins is used to form a scaffold for the bind-
ing of single-stranded DNA (Figure 10.8b and c). Interestingly, the OB fold also occurs in many
RNA-binding proteins, such as the transfer RNA synthetases (Section 10.9.3) and key ribonucleases that
process and turnover targeted RNA.
What is especially remarkable about the structure of the yeast Pot1 protein/DNA complex is that the
single-stranded DNA itself participates in the recognition, by folding back to make intra-molecular G T
base pairs and base-to-phosphate hydrogen bonds. Disruption of the base pairing, for example by substi-
tuting a guanosine base for inosine (and so replacing an exocyclic amino group by a keto group), decreases
the binding affinity by the equivalent of roughly 12kJmol^1. The fold of the DNA presents some of the bases
for stacking on aromatic and aliphatic side chains of the protein. The mode of interaction may be con-
served in Pot1 homologues from other organisms, including the human protein.
Protein–Nucleic Acid Interactions 397
Figure 10.8 The OB fold and single-stranded DNA recognition. (a) The ‘protection of telomere’ protein (Pot1) from
the fission yeast, Schizosaccharomyces pombe (PDB: 1QZG). (b) The Oxytrichia nova telomere end
binding protein (TEBP) bound with specific DNA (PDB: 1K8G). The Pot1 and TEBP proteins bind
single-stranded 3overhang at the termini of chromosomes. (c) The human Rep protein (PDB: 1JMC).
The common OB core for all three proteins is shown in red and pink for comparison. The single-stranded
DNA is shown in black