Structural studies have revealed how integrins become adhesive.

Integrins are a family of proteins of central importance in biology. They are 'sticky' molecules, gluing cells and tissues together. They are crucial in development, are involved in many processes in adults and have been implicated in several disease states. Their stickiness depends on their activation, which can be triggered by many signalling pathways within the cell. All these pathways, however, converge on one key protein: talin.

Talin binds to integrins through a special region known as the PTB (phosphotyrosine-binding) domain. Even though several other proteins have a PTB domain, and can bind integrins, they do not activate them. Now, a team led by Iain Campbell at the University of Oxford has determined the structural basis of this difference.

Nuclear magnetic resonance studies revealed that talin contains an additional domain that latches onto integrins close to the cell membrane; neighbouring parts of talin interact with the membrane itself. When these interactions were blocked, talin was no longer able to activate integrin-based adhesion.

The authors suggest that when talin binds an integrin, it alters the interactions between proteins in integrin dimers, changing the overall adhesive properties. As well as revealing a fundamental biological mechanism, the work opens up the prospect of targeted disruption of integrin activation, which could be therapeutically useful in several disease processes.

Image: Talin (yellow) binds to beta integrin tails (red); Kate Wegener using the program Moimol

External links

• Wegener KL et al. Structural basis of integrin activation by talin. Cell 2007;128(1):171–82.