DP fragments (red) of CDK2 cannot be seen in its inhibited form (left) but come into view (right) when cyclin (yellow) activates the kinase.
GODZIK/ELSEVIER
Ordered parts of protein structures can be revealed by crystallography, while disorder is usually hidden. Occasionally, solving a structure under a new condition reveals previously unseen protein parts. Scientists usually consider the exposure an improvement, especially if a new structure is obtained at a better resolution, and might even discard previous “inferior” models.
“I believe that's wrong,” says Godzik. “Different conditions have changed the protein; these are independent experiments.” In the new work, his group compared independently solved—previously thought of as redundant—crystal structures from the Protein DataBank. “As far as I know, the idea is new,” says Godzik. “And once you have the epiphany, you can see so many new things.”
What the authors saw were peek-a-boo fragments that only appeared structured under certain conditions. Such DP fragments were common; 50% of the examined proteins had at least one DP fragment, based on the authors' conservative definition.
Many proteins are also fully disordered and can become ordered upon major events, such as the binding of a protein partner. But the DP regions—which often coincided with regulatory regions—need a smaller push. “They are sitting on the edge of stability,” says Godzik. “Phosphorylation, small molecule binding, or even a local environmental change could all give them structure.”
The induced structure might have big effects on protein activity. Godzik uses protease-mediated activation as an example. “Things that are floppy are easier to cut,” he says. “So make the substrate stiffer by phosphorylating it, and you can block that [and prevent its activation].”
DP fragments had their own unique amino acid characteristics that set them apart from intrinsically disordered and fully ordered proteins. They favored a few specific types of residues and were more likely to pair a hydrophobic residue next to a charged one. This schizophrenic trait might help them easily cross the stability border. 
Reference:
