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Why do polypeptides undergo N-terminal acetylation and C-terminal amidation modification?

N-terminal acetylation and C-terminal amidation are common post-translational modifications (PTMs) that occur to polypeptides. These modifications play important roles in the stability, function, and trafficking of proteins. Here's why polypeptides undergo N-terminal acetylation and C-terminal amidation:

  1. N-terminal Acetylation:

    • Protein Stability: N-terminal acetylation often occurs co-translationally and is a widespread modification. It involves the addition of an acetyl group to the amino group at the N-terminus of a polypeptide. This modification stabilizes the protein against degradation by proteases.
    • Influence on Protein Interactions: N-terminal acetylation can influence protein-protein interactions. It may affect the ability of a protein to bind to other molecules, such as nucleic acids or other proteins.
  2. C-terminal Amidation:

    • Stability Enhancement: C-terminal amidation involves the conversion of the C-terminal carboxyl group into an amide. This modification is crucial for the stability of certain peptide hormones and neuropeptides. Amidation protects the peptide from degradation by exopeptidases.
    • Biological Activity: In many cases, amidation is required for the full biological activity of neuropeptides and hormones. The amidation of the C-terminus is often involved in receptor binding and signal transduction.
    • Cell Trafficking: Amidation can influence the intracellular trafficking of proteins. For example, amidation is common in peptides destined for secretion, and it may play a role in guiding these peptides through the secretory pathway.

These modifications are enzymatically catalyzed processes. For example, N-terminal acetylation is catalyzed by N-terminal acetyltransferases (NATs), while C-terminal amidation is catalyzed by enzymes like peptidylglycine alpha-amidating monooxygenase (PAM).

It's important to note that not all proteins undergo these modifications, and the presence or absence of N-terminal acetylation or C-terminal amidation can influence the biological functions of specific proteins. Overall, these modifications contribute to the structural diversity and functional complexity of the proteome.

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