Question

Compare the hemoglobin sequences on the following page and then answer parts A-C. Part A) Is there any difference in the amino acid sequence of the alpha subunits in normal and sickle cell hemoglobin? If yes, which amino acids are different? (Count the amino acids by their order in the sequence – first, second, third...) What amino acid or acids are in the normal alpha subunit and what amino acid or acids are in the sickle cell amino acid? Part B)Is there any difference in the amino acid sequence of the beta subunits in normal and sickle cell hemoglobin? If yes, which amino acids are different? (Count the amino acids by their order in the sequence - first, second, third...) What amino acid or acids are in the normal alpha subunit and what amino acid or acids are in the sickle cell amino acid? Part C) All of the differences in the way normal and sickle cell hemoglobin functions is because of the amino acid sequence changes you found. The symptoms of sickle cell anemia are all caused by these amino acid sequence changes. What about the difference between normal and sickle cell hemoglobin protein amino acid sequence is surprising? Normal Human Hemoglobin Alpha Subunit Amino Acid Sequence VLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHG KKVADALTNAVAHVDDMPNAL SALSDLHAHKLRVDPVNEKLLSHCLLVTLAAHLPAEFTP AVHASLDKFLASVSTVLTSKYR Sickle Cell Hemoglobin Alpha Subunit Amino Acid Sequence VLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHG KKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNEKLLSHCLLVTLAAHLPAEFTP AVHASLDKFLASVSTVLTSKYR Normal Human Hemoglobin Beta Subunit Amino Acid Sequence VHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPK VKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFG KEFTPPVQAAYQKVVAGVANALAHKYH Sickle Cell Hemoglobin Beta Subunit Amino Acid Sequence VHLTPVEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPK VKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFG KEFTPPVQAAYQKWAGVANALAHKYH

Answer 1

Answer: PartA) No, there is no difference in the amino acid sequence of the alpha subunits in normal and sickle cell hemoglobin.

PartB) Yes, there is a difference in the amino acid sequence of the beta subunits in normal and sickle cell hemoglobin. There is a change in the sixth position amino acid present in the beta subunit. In case of normal hemoglobin beta subunit, Glutamate is present at position 6 which is replaced by a Valine in case of sickle cell hemoglobin beta subunit.

PartC) In case of sickle cell hemoglobin, glutamate is replaced by valine at the 6th position of the hemoglobin beta chain. This means that a negatively charged polar amino acid (glutamate) is replaced by a nonpolar amino acid (valine) which may create a hydrophobic spot. This abnormal valine interacts with other nonpolar amino acids of the adjacent sickle cell beta subunit resulting in polymerization of hemoglobin tetramer. This polymerization of hemoglobin disrupts the structure of red blood cells and induced the formation of an abnormal sickle shaped red blood cell.