Spectrin interactions with globin chains in the presence of phosphate metabolites and hydrogen peroxide: implications for thalassaemia.
We have shown the differential interactions of the erythroid skeletal protein spectrin with the globin subunits of adult haemoglobin (HbA); these indicate a preference for alpha-globin over that for beta-globin and intact HbA in an adenosine 5'-triphosphate (ATP)-dependent manner. The presence of Mg/ATP led to an appreciable decrease in the binding affinity of the alpha-globin chain to spectrin and the overall yield of globin-spectrin cross-linked complexes formed in the presence of hydrogen peroxide. Similar effects were also seen in the presence of 2-,3-diphosphoglycerate (2,3 DPG), the other important phosphate metabolite of erythrocytes. The binding affinity and yield of cross-linked high molecular weight complexes (HMWCs) formed under oxidative conditions were significantly higher in alpha-globin compared with intact haemoglobin, HbA and the beta-globin chain. The results of this study indicate a possible correlation of the preferential spectrin binding of the alpha-globin chain over that of the beta-globin in the haemoglobin disorder beta-thalassaemia.
Datta
Poppy
P
Biophysics Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata 700064, India.
Chakrabarty
Sudipa
S
Chakrabarty
Amit
A
Chakrabarti
Abhijit
A
D019794:2,3-Diphosphoglycerate / Q000097:blood / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000097:blood / Q000378:metabolism*; D000818:Animals; D005914:Globins / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood / Q000378:metabolism*; D021122:Protein Subunits / Q000097:blood / Q000378:metabolism; D012756:Sheep; D013049:Spectrin / Q000378:metabolism*; D013789:Thalassemia / Q000097:blood*
D021122:Protein Subunits; D013049:Spectrin; D019794:2,3-Diphosphoglycerate; D000255:Adenosine Triphosphate; D005914:Globins; D006861:Hydrogen Peroxide