Question

Mutation and Protein Function Suppose that the gene for a protein 500 amino acids in length undergoes a mutation. If the mutation causes the synthesis of a mutant protein in which just one of the 500 amino acids is incorrect, the protein may lose all of its biological function. How can this small change in a protein's sequence inactivate it?

Short answer

A single amino acid change can alter a protein's structure, affecting its stability and function, leading to inactivation.

Step-by-step solution

Understanding Protein Structure

Proteins are made of long chains of amino acids, and their function is directly related to their three-dimensional structure. A protein's structure is mainly determined by the sequence of amino acids, which dictates how the protein will fold and interact with other molecules.

Analyzing the Impact of a Single Mutation

A single amino acid substitution can significantly alter the protein's structure. Even if only one out of 500 amino acids is incorrect, it can cause changes in the local environment or folding pattern, potentially leading to the protein adopting a non-functional shape.

Protein Folding and Function Relationship

The specific three-dimensional shape of a protein is crucial for its biological activity. A change in one amino acid can disrupt critical interactions that are necessary for maintaining the protein's functional conformation, such as hydrogen bonding or hydrophobic interactions.

Example of Mutation Effects

For example, if a hydrophobic amino acid is replaced by a hydrophilic one, it can disrupt the protein's core hydrophobic interactions, leading to improper folding. Alternatively, if a key residue at an active site is altered, the protein might lose its ability to bind to its substrate or another biological molecule.

Conclusion

Thus, even a single amino acid change in the protein sequence can lead to profound effects on protein stability and function, possibly resulting in loss or alteration of biological activity.

Key concepts

Amino Acid Substitution

Amino acid substitution refers to the replacement of one amino acid in a protein with another. This seemingly small change can drastically impact a protein's function. Proteins are composed of long chains of amino acids, each with distinct chemical properties. A single amino acid substitution may happen due to a mutation. This change might lead to either a positive adaptation or a detrimental effect, depending on where in the protein it occurs.

One common consequence of amino acid substitution is the alteration of the protein's shape or function. For example, replacing a hydrophobic amino acid with a hydrophilic one can affect how the protein folds and interacts with other molecules. Such a change can prevent a protein from functioning correctly, as seen in several genetic diseases caused by point mutations.

• Hydrophobic amino acids tend to be buried inside the protein's structure, while hydrophilic ones are often found on the surface.
• A change in amino acid may affect the protein's ability to interact with other proteins or cellular structures.
• Some substitutions could lead to protein misfolding, resulting in diseases like cystic fibrosis or sickle cell anemia.

Protein Structure

The protein structure is fundamental to its biological function and is determined by the sequence of amino acids. Proteins have four levels of structure that define their shape and function.

The primary structure is the linear sequence of amino acids linked by peptide bonds. The secondary structure refers to local folding within a polypeptide, forming structures such as alpha helices or beta sheets. The tertiary structure is the overall three-dimensional shape of a protein, resulting from interactions among the side chains. Lastly, the quaternary structure arises when multiple protein chains (subunits) come together.

• Each level of structure contributes to the protein's stability and its unique function.
• Incorrect folding at any level can lead to dysfunctional proteins.
• Mutations can disrupt the delicate balance of forces maintaining these structures, causing loss of function.

Protein Folding

Protein folding is the process by which a protein achieves its functional three-dimensional structure. This process is driven by the amino acid sequence and involves multiple steps facilitated by molecular forces such as hydrogen bonding and hydrophobic interactions.

Proper folding is essential for protein functionality. The final structure allows proteins to bind with other molecules and perform their biological roles. Incorrect folding can lead to non-functional proteins, often aggregated within the cell, sometimes resulting in disease.

• Misfolded proteins can form toxic aggregates, as seen in neurodegenerative diseases like Alzheimer's.
• Chaperone proteins often assist in correct folding.
• The environment can also impact folding, where conditions such as pH and temperature are crucial.

Biological Function of Proteins

Proteins play vital roles in almost every biological process, and their function is as diverse as their structures. They are essential for processes like catalysis, signaling, transport, and structural support.

Enzymes, a type of protein, catalyze biochemical reactions, significantly speeding them up. Hormones, another protein classification, function as signaling molecules, coordinating physiological processes. Proteins like hemoglobin transport oxygen, while others form structural elements, such as collagen in connective tissues.

• The unique structure of each protein enables its specific function.
• Any alterations in structure, like those due to a mutation, can impair functional efficiency or entirely halt activity.
• Understanding protein structure and function relationships is crucial for biotechnological applications and drug design.