Question

Transthyretin has a role in the transport of hormone thyroxine and retinol in blood.

(a) Compare and contrast the mechanism of transthyretin-mediated thyroxine and retinol transport.

(b) Mutations in transthyretin can lead to familial amyloid polyneuropathy. Briefly explain the underlying mechanism.

Answer 1

Ans (a)- Transthyretin mediated thyroxin transport-Transthyretin transports only about 15% of plasma T4 . In CSF , it is the major T4 carrier. At the structural level, two identical binding sites for T4 are located in the central channel of Transthyretin tetramer .Each tetramer carries no more than 1 T4 molecule.

Transthyretin mediated retinol transport- Retinol or Vitamin A circulates in the plasma bound to Retinol binding protein(RBP) . In the plasma RBP-retinol is found in complex with Transthyretin. The loaction of Transthyretin binding sites for RBP is revealed in the crystal structure of the complex. One Transthyretin tetramer can bind to two RBP molecules.

Ans 2- Mutation in Transthyretin gene destabilize Transthyretin protein to misfold from its native tetramer form to amyloidogenic monomer form. Transthyretin related Familial amyloid polyneuropathy is a life threatening disease caused by accumulation of amyloidogenic Transthyretin protein in tissues.