2.14 Significance of Amino Acid Sequence

The sequence of amino acids in a polypeptide chain constitutes the primary structure of a protein. This specific sequence is critical as it dictates the protein's final three-dimensional shape and, consequently, its biological function. The sequence is genetically determined by the sequence of nucleotides in DNA. A minor change, such as a point mutation (a change in a single nucleotide), can alter the amino acid sequence, leading to a dysfunctional protein and potentially severe diseases.

Frederick Sanger was the first scientist to determine the amino acid sequence of a protein molecule, specifically Insulin. He concluded that proteins have a specific chemical characteristic due to their precise sequence of amino acids.

Normal Hemoglobin (HbA)

• Function: An iron-rich protein in red blood cells that carries oxygen from the lungs to the rest of the body.
• Structure: Composed of four polypeptide chains:
  • Two alpha (α) chains, each with 141 amino acids.
  • Two beta (β) chains, each with 146 amino acids.
• Total Amino Acids: A single hemoglobin molecule contains 574 amino acids ($141\times 2+146\times 2=574$).
• Associated Red Blood Cells: Normal red blood cells are disc-shaped (biconcave), flexible, and move easily through blood vessels.

Sickle Cell Anemia and Sickle Hemoglobin (HbS)

Sickle cell anemia is a hereditary disease that serves as a classic example of how a single amino acid change can have drastic consequences.

• Cause: A point mutation in the gene that codes for the beta-chain of hemoglobin.
• Molecular Change: This mutation causes a single amino acid substitution at the sixth position of the beta-chain: Glutamic acid is replaced by Valine.
• Resulting Protein: The abnormal hemoglobin is called sickle hemoglobin or HbS.
• Effect on Red Blood Cells: HbS causes red blood cells to deform into a sickle or crescent shape. These cells are stiff, sticky, and fragile.
• Physiological Consequences:
  • Sickle cells can block blood flow in small blood vessels.
  • This blockage can lead to severe pain, tissue and organ damage, and other serious complications.

Functional Importance

The primary structure is crucial for the protein's proper folding into its functional three-dimensional shape. This illustrates the profound impact that a small change at the molecular level can have on the overall health and physiology of an organism. The amino acid sequence is itself encoded by the nucleotide sequence of a gene in DNA — a concept central to molecular biology and genetics.