Compare the Difference Between Similar Terms

What is the Difference Between N-terminus and C-terminus

Dr.Samanthi

Once the protein chain is completed in the protein synthesis, one end of the protein will have a free amine group, and the other end will have a free carboxylic acid group. N-terminus and C-terminus are two opposite ends of the polypeptide chain.

The key difference between N-terminus and C-terminus is their position. N-terminus is the free amine end of the polypeptide chain, while C-terminus is the free carboxylic acid end of the polypeptide chain.

CONTENTS

1. Overview and Key Difference
2. What is N-terminus
3. What is C-terminus
4. Similarities – N-terminus and C-terminus
5. N-terminus vs C-terminus in Tabular Form
6. Summary – N-terminus vs C-terminus
7. FAQ – N-terminus and C-terminus

What is N-terminus?

The N-terminus, also known as the amino-terminus, NH2-terminus, or amine-terminus, is the start of a polypeptide chain. It has a free amine group (-NH2). In protein nomenclature, peptide sequences are typically written from the N-terminus to the C-terminus, aligning with the direction of translation and the text.

When a protein is translated from mRNA, it is created from the N-terminus to the C-terminus. The N-terminus performs numerous functions. The N-terminus is the first part of the protein that exits the ribosome during protein biosynthesis. The N-terminus normally contains signal peptide sequences called “intracellular postal codes” that direct the delivery of the protein correctly to the proper organelle.  Furthermore, the N-terminus can be modified post-translationally, such as the removal of initiator methionine (iMet) by aminopeptidases, attachment of small chemical groups like acetyl, propionyl, and methyl, and the addition of membrane anchors like palmitoyl, and myristoyl groups.

What is C-terminus?

The C-terminus, also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, or COOH-terminus, is the end of an amino acid chain or polypeptide that is terminated by a free carboxyl group (-COOH).

The C-terminus of the polypeptide contains retention signals for protein sorting. The most common ER retention signal is the amino acid sequence KDEL (Lys-Asp-Glu-Leu) or HDEL (His-Asp-Glu-Leu) at the C-terminus of the polypeptide. This signal keeps the protein in the endoplasmic reticulum, which prevents it from entering the secretory pathways. Furthermore, the C-terminus of proteins can be modified post-translationally. An example is the addition of a lipid anchor to the C-terminus that allows the protein to be inserted into a membrane without having a transmembrane domain.

Similarities Between N-terminus and C-terminus

  1. N-terminus and C-terminus are two opposite ends of the polypeptide chain.
  2. Both are made up of amino acids.
  3. Both are extremely important for the protein function.
  4. They are composed of signal sequences.

Difference Between N-terminus and C-terminus

Definition

  1. The N-terminus is defined as the start of a polypeptide chain.
  2. The C-terminus is defined as the end of a polypeptide chain.

Other Names

  1. The N-terminus is also referred to as the amino-terminus, NH2-terminus, or amine-terminus.
  2. The C-terminus is also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, or COOH-terminus.

Free Group Contains

  1. The N-terminus contains a free amine group (-NH2).
  2. The C-terminus contains a free carboxyl group (-COOH).

Signal Sequence

  1. The N-terminus contains intracellular postal codes.
  2. The C-terminus may contain ER retention signals such as the amino acid sequence KDEL (Lys-Asp-Glu-Leu) or HDEL (His-Asp-Glu-Leu).

Function

  1. The N-terminus directs the correct delivery of the protein to the proper organelle.
  2. The C-terminus keeps the protein in the endoplasmic reticulum, preventing it from entering the secretory pathways.

Modifications

  1. The N-terminus can be modified post-translationally, such as removal of initiator methionine (iMet) by aminopeptidases, attachment of small chemical groups like acetyl, propionyl, and methyl, and addition of membrane anchors like palmitoyl and myristoyl groups.
  2. The C-terminus can be modified post-translationally, for example, by adding a lipid anchor that allows the protein to be inserted into a membrane without having a transmembrane domain.

The infographic below presents the differences between N-terminus and C-terminus in tabular form for side-by-side comparison.

Summary – N-terminus vs C-terminus

The N-terminus and C-terminus are two opposite ends of the polypeptide chain. N-terminus is also known as the amino-terminus, NH2-terminus, or amine-terminus, while C-terminus is also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, or COOH-terminus. N-terminus is the start of a polypeptide chain, whereas C-terminus is the end of a polypeptide chain. Thus, this is the key difference between N-terminus and C-terminus.

FAQ: N-terminus and C-terminus

1. How can you differentiate the N-terminus of a protein from the C-terminus?

    • Protein sequences are written from the end with the free -NH3+ group to the end with the free -COO- group. The end with the free -NH3+ group is called the N-terminus, while the end with the free -COO- group is called the C-terminus.

2. What are the C and N-terminus in translation?

    • During translation, when a protein is synthesized from messenger RNA, it is typically created from the N-terminus to the C-terminus. The amino end of an amino acid on a charged tRNA during the elongation stage of translation usually attaches to the carboxyl end of the growing chain.

3. What are the modifications that happen in the N-terminus and C-terminus?

    • The N-terminus can undergo post-translational modifications such as the removal of initiator methionine (iMet) by aminopeptidases, attachment of small chemical groups like acetyl, propionyl, and methyl, and the addition of membrane anchors like palmitoyl and myristoyl groups. The C-terminus can be post-translationally modified by the addition of a lipid anchor to the C-terminus end.

4. What are the main functions of the N-terminus and C-terminus?

    • The N-terminus directs the delivery of the protein correctly to the proper organelle, while the C-terminus retains the protein in the endoplasmic reticulum, preventing it from entering the secretory pathways.
Reference:

1. “N & C Terminal Sequencing: Amino Acid Sequence Analysis.” BioPharmaSpec.
2. “Terminal Amino-Acid Residue.” Science Direct.

Image Courtesy:

1. “22 N-terminal amino acid sequence” By BQUB19 CGinard – Own work (CC BY-SA 4.0) via Commons Wikimedia
2. “C-terminal of protein” By I, Danielle dk (CC BY-SA 3.0) via Commons Wikimedia

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