Transplanting a unique allosteric effect from crocodile into human haemoglobin

Abstract

Crocodiles are able to remain under water for more than one hour without surfacing to breathe and often kill their prey by drowning it. How do crocodiles stay under water for a long time? When they hold their breath, bicarbonate ions, the final product of respiration, accumulate and drastically reduce the oxygen affinity of haemoglobin, releasing a large fraction of haemoglobin-bound oxygen into the tissues. We have now located the bicarbonate-ion-binding site at the alpha 1 beta 2-subunit interface by making various human-crocodile chimaeric haemoglobins. Furthermore, we have been able to transplant the bicarbonate effect into human haemoglobin by replacing only a few residues, even though the amino-acid sequence identity between crocodile (Crocodylus niloticus) and human haemoglobins is only 68% for the alpha- and 51% for the beta-subunit. These results indicate that an entirely new function which enables species to adapt to a new environment could evolve in a protein by a relatively small number of amino-acid substitutions in key positions.