With Some Interacting Proteins, a kiss comes before a Hug

In work that helps elucidate how proteins recognize each other, researchers have found conclusive evidence that two interacting proteins about to form a complex first give each other a slightly off-target kiss, metaphorically speaking, before joining in their ultimate embrace. Marius Clore and coworkers at the National Institute of Diabetes & Digestive & Kidney Diseases used a technique called paramagnetic relaxation enhancement to detect and visualize transient "pre-encounter complexes" that precede and facilitate formation of a stable complex between the N-terminal domain of enzyme I and the phosphocarrier protein HPr (Nature 2006, 444, 383). The pre-encounter complexes form as a result of long-range electrostatic attraction, and possibly also short-range van der Waals interactions, between the proteins. These pre-encounters put the proteins' binding sites in close proximity, making it easy for them to "find" each other later. The technique revealed similar pre-encounters between two other protein-protein complexes, suggesting that the interaction may reflect a general phenomenon.