Question

In the course of evaluating a 6-year-old patient with bronchitis, a systematic hematological study of the child’s blood was performed. An abnormal protein was detected and additional tests on the patient’s blood sample were performed. These tests, which included isoelectric focusing, electrophoresis, and cation-exchange, high-performance liquid chromatography, confirmed the existence of a novel blood protein. The protein was also observed in blood samples from the child’s father and other blood relatives, indicating a genetic basis for the abnormality. The abnormal protein was isolated in a pure form and the following amino acid sequence was determined: 1 VLSPADKTNV KAAWGKVGAH AGEYGAEALE RMFLSFPETT KTYFPHFDLS 51 HGSAQVKGHG KKVADALTNA VAHVDDMPNA LSALSDLHAH KLRVDPVNFK 101LLSHCLLVTL AAHLPAEFTP AVHASLDKFL ASVSTVLTSK YR

A. Identify this novel blood protein. What does the analysis tell you about the identity of the protein?

B. The molecular mass of the abnormal blood protein is approximately 100 daltons more than the mass of the “normal” protein. What does this suggest about the normal protein, and what might you do to verify your hypothesis?

C. What information can you find on the secondary, tertiary, and quaternary structure of the “normal” version of the protein?

Answer 1

Answer:

A) Identify this novel blood protein. What does the analysis tell you about the identity of the protein?

This protein is a mutated form of alpha chain of hemoglobin protein with insertion of an additional amino acid Glutamic acid (E) at position 38th due to which the molecular mass of the abnormal protein has increased by ~100 daltons compared to mass of normal alpha chain of hemoglobin.

B. The molecular mass of the abnormal blood protein is approximately 100 daltons more than the mass of the “normal” protein. What does this suggest about the normal protein, and what might you do to verify your hypothesis?

The normal protein as discussed above is alpha chain of hemoglobin protein. Normal version of this protein consists of 141 amino acids, where as the mutated version in this case consists of 142 amino acids (one additional amino acid due to insertion mutation at position 38)

C. What information can you find on the secondary, tertiary, and quaternary structure of the “normal” version of the protein?

The structure of the normal version of this protein (alpha chain of hemoglobin is mentioned below)

• Hemoglobin molecule is a tetramer consisting of 2 identical alpha and 2 identical beta chains (total four polypetide chains) which are held together by intermolecular interactions and has a globular shape.
• The alpha chain clusture for hemoglobin molecule is located on chromosome 16
• A normal alpha chain of hemoglobin molecule consists of 141 amino acids