Structural studies have revealed how two hormone delivery proteins ferry their cargo.

Thyroxine and corticosteroid hormones are carried through the bloodstream attached to delivery molecules (globulins). Surprisingly, these globulins are part of the serpin family, protease inhibitors involved in a wide range of body functions, including blood clotting.

Randy Read, Robin Carrell and colleagues at the Cambridge Institute for Medical Research have discovered how the globulins' structures can account for this major shift in function.

Serpins act as characteristic 'molecular mousetraps' in which a large section of the protein swings over to clamp a protein target in its active site. In the hormone-transporting globulins, however, a peptide loop at the active site can readily move in and out, but in a much less dramatic way than in other serpins, owing to a change at a key amino acid position.

When the loop moves, it triggers a conformational change within the binding pocket, causing the hormone to be squeezed off the carrier. The loop thus acts as a kind of flip-flop, in which the hormone is either bound tightly or released.

The delivery proteins thus seem to have adapted the original protease inhibitory mechanism, using a less dramatic conformational change for completely different ends.

• This research was supported by the Wellcome Trust, the British Heart Foundation and the Alpha-1 Foundation.

Image: Structure showing how thyroxine is carried in the blood in a surface pocket on its binding globulin. Courtesy of Robin Carrell.

External links

• Zhou A et al. Structural mechanism for the carriage and release of thyroxine in the blood. Proc Natl Acad Sci USA 2006;103(36):13321–6.