these loops connect strands of a -sheet in a globular domain of the DNA-binding protein, and they pene-
trate deeply into major and/or minor grooves, where the side chains make hydrogen-bonding and van der
Waals contacts with the bases, sugars and phosphates. This type of interaction is also very effective for achiev-
ing shape complementarity and for the optimization of buried surface area in the complex. Examples of
this type of interaction come from the extensive family of proteins with a -layer structure, as represented
by the Rel and Stat proteins (Figure 10.7). The effectiveness of the mode of interaction of these proteins is
shown in their specificity and very high binding constants (dissociation constants typically of 10^9 M).
Loops are also used by many restriction endonucleases, in conjunction with other structural elements,
to embrace the target DNA and to activate hydrolytic attack of the phosphate backbone (Section 10.5).
10.3.8 Single-Stranded DNA Recognition
Single-stranded DNA does not fold into the same compact structure as duplex DNA, and it is consequently
much more flexible. The hydrophobic bases are more readily exposed and these are targets for interaction with
the protein. Consequently, most single-stranded DNA-binding proteins have surface patches that are positively
charged, to match the phosphate backbone, as well as patches, which are hydrophobic, so as to match the bases.
The ‘protection of telomere’ protein (Pot1) provides an example of single-stranded DNA recognition
(Figure 10.8a). This protein binds to the termini of eukaryotic chromosomes, known as telomeres, which have
single-stranded 3-overhangs of a G/T rich, repetitive sequence. The structural motif used by Pot1 is the widely
396 Chapter 10
Figure 10.7 Loops and miscellaneous folds. Representative complexes from the Rel and Stat protein fold families.
The Rel proteins, such as p50, can form heterodimers on different DNA elements. Here, the p50 (black) /p65
(red) heterodimer is shown (PDB: 1LE5)