C-terminus

C-terminus or carboxyl-terminus is a term used in protein biology to refer to the end of an amino acid chain (polypeptide) which terminates in a free carboxyl group (-COOH). Proteins are synthesized by ribosomes in a process known as translation, where messenger RNA (mRNA) is decoded to produce a specific sequence of amino acids. The C-terminus is the end of the amino acid chain that is synthesized last, opposite to the N-terminus, which contains a free amino group (-NH2) and is synthesized first. The sequence of the protein is always read from the N-terminus to the C-terminus, reflecting the direction of synthesis and the orientation of the protein's primary structure.

Structure and Function

The structure of the C-terminus can influence the protein's stability, localization, and interaction with other molecules. For example, specific sequences at the C-terminus can act as signal peptides, directing the protein to specific locations within the cell, such as the nucleus, mitochondria, or endoplasmic reticulum. Additionally, the C-terminus can participate in the regulation of protein activity through post-translational modifications such as phosphorylation, ubiquitination, and acetylation. These modifications can affect the protein's function, its interactions with other proteins, and its degradation.

Post-Translational Modifications

Post-translational modifications (PTMs) at the C-terminus play critical roles in the regulation of protein function. For instance:

- Phosphorylation: The addition of a phosphate group, often modulates the activity of enzymes and signaling proteins. - Ubiquitination: The attachment of ubiquitin molecules, targeting the protein for degradation by the proteasome. - Acetylation: The addition of an acetyl group, can influence protein stability and interactions with other molecules.

C-Terminal Sequences and Targeting Signals

Certain C-terminal sequences act as targeting signals, directing the protein to its appropriate location within the cell. These include:

- Nuclear Localization Signals (NLS): Direct proteins to the nucleus. - Mitochondrial Targeting Sequences (MTS): Guide proteins to the mitochondria. - ER Retention Signals: Retain proteins in the endoplasmic reticulum.

Clinical Significance

Alterations in the C-terminus of proteins can lead to diseases. For example, mutations that affect the C-terminal targeting signals can result in mislocalization of proteins, contributing to the pathology of various diseases, including cancer and neurodegenerative diseases. Furthermore, the C-terminus is a target for the development of therapeutic agents, as modulating the interactions or modifications at this site can influence the activity and stability of pathologically relevant proteins.

Research Tools

In research, synthetic peptides corresponding to the C-terminal sequences of proteins are often used as tools for studying protein-protein interactions, as well as for the development of antibodies that specifically recognize the C-terminus of proteins.

See Also

• Protein structure
• Protein biosynthesis
• Post-translational modification
• N-terminus