A few residues (indicated) tie PINCH-1 and Nck-2 together weakly.


Jun Qin (Lerner Research Institute, Cleveland, OH) is the defender of the weak, or at least of weak protein–protein interactions. His work with Julia Vaynberg, Tomohiko Fukuda, Cary Wu (University of Pittsburgh, Pittsburgh, PA), and colleagues shows that an extremely weak affinity between two focal adhesion proteins is needed for cell migration.

The focal adhesion proteins are the adaptors PINCH-1 and Nck-2, whose weak interaction (KD ≈ 3 mM) was noted previously in yeast two-hybrid assays but not with less sensitive techniques. Using NMR, which unlike crystallography provides structural information even for very weak interactions, the group has now determined the structure of the tiny interface between the adaptors. To prove its biological relevance, they then used genetic rescue experiments to show that the disruption of the PINCH-1/Nck-2 interface in vivo impairs cell spreading and migration.

The results show that the Nck-2/PINCH-1 interaction is necessary for processes that depend on focal adhesions. Focal adhesions, in which many other components are tightly bound, may rely on this weak interaction for dynamic assembly and disassembly.

For Qin, the results extend far beyond this one pair. “In humans,” he says, “there are hundreds of thousands of protein–protein interactions. They can't all be strong, or our cells would be glued together all the time.” As NMR-based studies on purified proteins is relatively quick and easy, the significance of other very weak interactions (e.g., cell–cell contacts and enzyme–substrate pairs) may be determined soon.


Vaynberg, J., et al.
Mol. Cell.