Evolutionary divergence of the trypanosome haptoglobin-haemoglobin receptor

A surprising case of functional divergence in a trypanosome receptor.

This unexpected story started when Harriet Lane-Serff was working to determine the structure of the Trypanosoma congolense haptoglobin-haemoglobin receptor bound to its haptoglobin-haemoglobin ligand. 

Harriet prepared the protein complex for crystallisation and was delighted when beautiful red crystals formed. But on solving the structure, she was puzzled to find that they contained a complex of the receptor bound to haemoglobin alone.

Harriet followed up this discovery by testing the binding of the receptor to haptoglobin-haemoglobin and to haemoglobin. As previously reported, the Trypanosoma brucei receptor, TbHpHbR binds to haptoglobin-haemoglobin but not to haemoglobin. However, Harriet found that the receptor from the closely related species Trypanosoma congolense, TcHpHbR bound most strongly to haemoglobin. Why does this receptor have such different binding properties in these two closely related trypanosome species?

Next, Paula McGregor, working with Mark Carrington, studied the role of the receptor during infection. While TbHpHbR is produced by trypanosomes found in mammalian blood, Paula discovered that TcHpHbR is instead produced by trypanosomes in the mouthparts of an infected tsetse fly. It is likely that this allows trypanosome to harvest haemoglobin from lysed red blood cells which are ingested when the tsetse fly takes a blood meal.

These two species of African trypanosome therefore use their haemoglobin-haptoglobin receptor during different stages of their life cycles and for acquisition of different ligands, providing a remarkable example of evolutionary divergence. 

Lane-Serff, H., MacGregor, P., Peacock, L., Macleod, O.J., Kay, C., Gibson, W., Higgins, M.K.^* and Carrington, M.^* (2016) Evolutionary diversification of the trypanosome haptoglobin-haemoglobin receptor from an ancestral haemoglobin receptor. eLife 5 e13044