Which of the following best describes how the N-terminal rule is associated with protein stability? Choose one:
A. The termination of a protein is dependent on a certain time (N).
B. An asparagine (N) at the end of a protein decreases its half-life.
C. An increased number (N) of aspartic and/or glutamic acids in a protein decreases its stability.
D. The amino-terminal amino acid of a protein correlates with its stability.
E. The carboxy-terminal amino acid determines the approximate half-life of the protein.
The correct answer and explanation is:
The correct answer is: D. The amino-terminal amino acid of a protein correlates with its stability.
Explanation:
The N-terminal rule refers to the idea that the identity of the amino acid at the N-terminus of a protein (the first amino acid in the polypeptide chain) plays a significant role in determining the protein’s stability and its rate of degradation. This concept was first proposed by M. J. Varshavsky in the 1980s. According to the N-terminal rule, proteins that start with specific amino acids are more likely to be rapidly degraded, while others are more stable.
Proteins with certain N-terminal residues are recognized by the cellular machinery responsible for protein degradation, such as the proteasome. For example, proteins that start with arginine, leucine, phenylalanine, or tyrosine are typically unstable and are more likely to be targeted for degradation. Conversely, proteins that begin with alanine, serine, or glycine tend to be more stable and have longer half-lives.
This correlation between N-terminal amino acid identity and protein stability is important because it helps regulate protein levels within the cell. It ensures that only functional and necessary proteins are allowed to persist, while damaged or misfolded proteins are quickly removed. Additionally, the N-terminal rule can be modified by the presence of specific signaling events or post-translational modifications that influence protein stability.
Understanding the N-terminal rule helps in research related to protein turnover, disease states involving abnormal protein degradation (such as neurodegenerative diseases), and the development of therapeutic strategies targeting specific proteins for degradation.