Transplanting a unique allosteric effect from crocodile into human haemoglobin

Area of Science:

• Biochemistry
• Physiology
• Evolutionary Biology

Background:

• Crocodiles exhibit remarkable diving abilities, remaining submerged for over an hour.
• This prolonged breath-holding is crucial for hunting, often involving drowning prey.

Purpose of the Study:

• To elucidate the molecular mechanism behind crocodiles' extended breath-holding capacity.
• To investigate the role of bicarbonate ions and hemoglobin in this adaptation.

Main Methods:

• Construction of human-crocodile chimeric hemoglobins.
• Analysis of bicarbonate-ion-binding sites.
• Functional characterization of modified human hemoglobins.

Main Results:

• The bicarbonate-ion-binding site was identified at the alpha 1 beta 2-subunit interface.
• The bicarbonate effect was successfully transferred to human hemoglobin by altering a few key residues.
• Minimal sequence identity (68% alpha, 51% beta) between crocodile and human hemoglobins belies functional adaptation.

Conclusions:

• Small changes in key amino acid positions can lead to significant functional evolution in proteins.
• This study provides a molecular basis for crocodile's unique physiological adaptation.
• Protein adaptation can enable species to thrive in diverse environments.