Oxidized alpha haemoglobin bound to alpha-haemoglobin-stabilizing protein (AHSP)
Homo sapiens (human)
Hemoglobin is an abundant protein in red blood cells. It performs the function of carrying oxygen to the various tissues in the body. It is present in all vertebrates and some invertebrates. Each hemoglobin molecule is made up of two alpha-globin chains (alphaHb) and two beta-globin chains (betaHb). Each of the four chains binds to a single heme molecule which binds oxygen. Thus each molecule of hemoglobin carries four molecules of oxygen. The free alphaHb and betaHb subunits are highly toxic with their heme irons producing reactive oxygen species (ROS) which have damaging effects in the cells. alphaHb is also liable to denature and produce the toxic alpha-globin polypeptide along with free heme and iron which in turn can produce ROS. The alpha-hemoglogin-stabilizing protein (AHSP) binds to Hb and prevents the formation of ROS from alphaHb under conditions of oxidative stress.
The structure here shows two oxidized alphaHb-AHSP complexes. Each complex consists of an elongated three-helix bundle AHSP and a seven-helix alphaHb. The heme molecule and AHSP bind the alphaHb on opposite sides. The complex of alphaHb-AHSP undergoes a conformational change with the oxidation of the iron atom. This results in a bis-histidyl configuration of the heme group where it is coordinated by both the proximal and distal histidines in alphaHb. This configuration protects the iron atom from the solvent and reduces its ability to act as a catalyst in redox reactions, thus preventing the formation of ROS. The alphaHb in complex with AHSP can also be recruited to form the tetrameric hemoglobin in the presence of betaHb.
Protein Data Bank (PDB)
author: Ashwini Patil