Question

Explain what happens if even one amino acid is substituted for another in a polypeptide chain. Provide a specific example.

Short answer

Answer: A single amino acid substitution in a polypeptide chain can potentially impact a protein's function by altering its structure, stability, or biological activity. For example, in sickle cell anemia, a single amino acid substitution in the hemoglobin protein (glutamic acid replaced by valine) causes a change in the protein structure, leading to the formation of long, rod-like aggregates. These aggregates cause red blood cells to become rigid and sickle-shaped, resulting in reduced oxygen-carrying capacity and various health complications.

Step-by-step solution

Introduction to Amino Acids and Polypeptide Chains

Amino acids are the building blocks of proteins, and a polypeptide chain is a sequence of amino acids linked by peptide bonds. The sequence of amino acids defines the primary structure of a protein, and it is crucial for the protein's eventual shape and function.

The Importance of the Amino Acid Sequence

The specific order of amino acids in a polypeptide chain determines the overall structure and function of the protein. Any change in this sequence may lead to an alteration in the protein's structure, stability, and biological activity. In some cases, even a single amino acid substitution can cause significant changes to the protein's functionality or lead to diseases.

The Effects of Amino Acid Substitution

The substitution of one amino acid for another can lead to different outcomes depending on the specific change. Some possible scenarios are: 1. The protein may still be functional, but its efficiency or activity may be altered. 2. The substitution may cause the protein to lose its function or become nonfunctional. 3. The protein may become misfolded, which can lead to aggregation and cellular toxicity. 4. The substitution may affect the protein's ability to interact with other molecules or cellular components.

A Specific Example: Sickle Cell Anemia

A well-known example of how a single amino acid substitution can impact a protein's function is sickle cell anemia. This genetic disorder is caused by a single amino acid substitution in the hemoglobin protein, which is responsible for carrying oxygen in the blood. In sickle cell anemia, the amino acid glutamic acid is replaced by valine in position 6 of the β-globin chain, causing a change in the protein structure. This single amino acid substitution alters the way the hemoglobin molecules interact with each other, resulting in the formation of long, rod-like aggregates. These aggregates cause the red blood cells containing the altered hemoglobin to become rigid and sickle-shaped, leading to reduced oxygen-carrying capacity and various health complications, such as anemia, pain, organ damage, and infections.

Key concepts

Protein Structure and Function

Proteins are fundamental workhorses within every cell, playing an array of roles from structural support to catalyzing reactions.

The specific sequence of amino acids in a polypeptide chain leads to the formation of complex three-dimensional structures, which are key to the protein's functionality. They fold into unique shapes that determine their interactions with other molecules, enabling them to execute tasks like transporting oxygen, signaling between cells, or defending the body against pathogens.

Any alteration in the sequence, such as an amino acid substitution, can result in a misshapen protein that does not function correctly, or can change the protein's characteristics entirely, affecting how it interacts with other molecules and influencing health.

Sickle Cell Anemia

Sickle cell anemia exemplifies the profound impact that a single amino acid substitution can have on protein function and human health.

This genetic disorder occurs when the amino acid valine replaces glutamic acid in the hemoglobin protein. This specific substitution leads to hemoglobin proteins sticking together and forming stiff fibers. As a result, red blood cells assume a sickle shape, leading to blockages in blood vessels and preventing proper oxygen transport, which can cause intense pain and organ damage.

It is a striking illustration of how delicate the balance is within biological systems and how critical the appropriate sequence of amino acids is for the maintenance of life.

Polypeptide Chain

A polypeptide chain is a linear sequence of amino acids bonded together by peptide bonds, the fundamental structure within a protein.

The chain folds in various ways, forming secondary structures like alpha-helices and beta-sheets, which further fold into the complex tertiary structures that give proteins their functionality. A single substitution in the amino acid sequence can prevent the polypeptide from adopting its intended structure, leading to inefficiency or complete loss of protein function, it's also an example of how intricate and interdependent protein structure is on its amino acid composition.

Genetic Disorders

Genetic disorders arise from mutations in the DNA sequence that can lead to aberrant proteins.

These mutations can be as simple as a single nucleotide polymorphism (SNP), which changes one base in the DNA sequence and can lead to a different amino acid being incorporated into a protein. Beyond sickle cell anemia, there are numerous other genetic disorders caused by such mutations, demonstrating that our genetic code is both remarkably robust and yet vulnerable to minute changes. Understanding the relationship between genetic mutations and protein structure helps in developing targeted treatments for these conditions.