Question

Can the change of a single amino acid in a polypeptide drastically alter the function of the polypeptide? Hint: use the hemoglobin molecule to answer this.

Short answer

Yes, the change of a single amino acid in a polypeptide can drastically alter its function. A prime example is the hemoglobin molecule in sickle cell anemia, where a mutation replaces glutamic acid (\(Glu\)) with valine (\(Val\)) at the sixth position of the beta-globin chain. This seemingly minor change affects the structure and function of hemoglobin, causing misshaped red blood cells and leading to painful episodes, organ damage, and other complications.

Step-by-step solution

Understanding the structure and function of polypeptides

A polypeptide is a chain of amino acids connected by peptide bonds. Polypeptides fold into specific three-dimensional shapes, which determines their function in a living organism. The sequence of amino acids in a polypeptide chain is directly related to its function and the overall protein structure.

Understanding amino acids

Amino acids are the building blocks of polypeptides. Each amino acid has a central carbon atom, an amino group (-NH2), a carboxyl group (-COOH), and a unique side chain (R group) that distinguishes it from other amino acids. There are 20 common amino acids present in polypeptides, and the combination and order of these amino acids determine the structure and function of the polypeptide.

The hemoglobin molecule

Hemoglobin is a metalloprotein found in red blood cells. Its primary function is to transport oxygen from the lungs to the body's tissues and carry carbon dioxide from the tissues back to the lungs. Hemoglobin is made up of four polypeptide chains: two alpha-globin chains and two beta-globin chains, each bound to a heme group containing an iron atom.

Single amino acid change in hemoglobin

An example of a single amino acid change in a polypeptide that significantly affects the function of that polypeptide is found in the disease called sickle cell anemia. In this case, the mutation occurs in the beta-globin chain of the hemoglobin molecule. Sickle cell anemia is caused by a point mutation in the gene that codes for the beta-globin chain. Specifically, the mutation replaces a glutamic acid (\(Glu\)) with a valine (\(Val\)) at the sixth position of the beta-globin chain. This seemingly minor change in the amino acid sequence drastically affects the structure and function of the hemoglobin molecule.

Effects of the amino acid change

As a result of this single amino acid change, hemoglobin molecules form an abnormal, rigid, and sickle-shaped structure, particularly when oxygen levels are low. These misshaped red blood cells can get stuck in blood vessels, blocking blood flow and leading to painful episodes, organ damage, and other complications. This example demonstrates that changing just one amino acid in a polypeptide can have a significant impact on the overall function and properties of the polypeptide. In this case, the altered hemoglobin molecule with the mutated beta-globin chain causes a serious genetic disorder, sickle cell anemia.

Key concepts

Understanding Amino Acids

Amino acids are fundamental components of polypeptides and proteins, serving as the essential building blocks for these biological molecules. Think of amino acids as individual beads on a string, where the string represents the polypeptide chain. Each of these 'beads' has a common structure: a central carbon atom, known as the \( \alpha \) carbon, flanked by an amino group (\(-NH_2\)), a carboxyl group (\(-COOH\)), and a unique side chain or R group. This R group is what makes each of the 20 standard amino acids unique and influences their chemical properties and how they interact with other molecules.

When amino acids link together through peptide bonds—a process called polymerization—they form the lengthy chains known as polypeptides. The order and combination of these amino acids in a polypeptide chain (also called the primary structure) are crucial. They dictate how the chain will fold into a final three-dimensional shape, which in turn determines the functionality of the protein. Errors in amino acid sequences can disrupt a protein's structure and lead to loss or alteration of function, which is sometimes associated with diseases.

The Structure of Hemoglobin

Hemoglobin is a quintessential example of a protein that depends on its structure for proper function. It's a complex protein found in our red blood cells, responsible for carrying oxygen from the lungs to the rest of the body and returning carbon dioxide back to the lungs for exhalation. The hemoglobin molecule's architecture is a tetramer, composed of two pairs of polypeptide chains: two alpha-globin and two beta-globin chains. Each of these chains is associated with a heme group featuring an iron atom that can bind oxygen.

The precise folding of these globin chains and their interaction with the heme, allows for hemoglobin's incredible oxygen-carrying capacity. The importance of each amino acid in maintaining hemoglobin's structure cannot be overstated. Even a single alteration can disrupt the entire molecule's stability and function, leading to conditions such as sickle cell anemia.

Sickle Cell Anemia and Hemoglobin Mutation

Sickle cell anemia powerfully illustrates the critical role of a single amino acid in a protein's function. This inherited blood disorder is the result of a single point mutation in the DNA that encodes the beta-globin chain of hemoglobin. Specifically, the mutation causes the sixth amino acid in the beta-globin chain to switch from glutamic acid (a negatively charged, hydrophilic molecule) to valine (a neutral, hydrophobic molecule).

This switch may seem small, but the replacement of just one hydrophilic amino acid with a hydrophobic one has a dramatic effect on the hemoglobin protein. Instead of remaining soluble, the mutated hemoglobin molecules tend to clump together, forming fibrous structures that deform the red blood cells into a sickle shape. These distorted cells can obstruct blood vessels, causing pain, potential organ damage, and various other serious health issues. This example poignantly shows how a single amino acid change can lead to a domino effect, with far-reaching implications for the health and wellbeing of an individual.