regulation of protein stability

Definition

Target type: biologicalprocess

Any process that affects the structure and integrity of a protein, altering the likelihood of its degradation or aggregation. [GOC:dph, GOC:mah, GOC:tb]

Protein stability regulation is a multifaceted process that ensures the proper functioning of cellular machinery. It involves a delicate balance between protein synthesis, folding, and degradation, tightly controlled by intricate molecular mechanisms.

**Protein Synthesis and Folding:**
- Translation of mRNA into a polypeptide chain marks the beginning of protein synthesis.
- Newly synthesized proteins must fold into their correct three-dimensional structures to become functional. This process, known as protein folding, is influenced by chaperone proteins that assist in proper folding and prevent aggregation.
- Folding is guided by interactions between amino acids, including hydrophobic interactions, hydrogen bonds, and electrostatic interactions.

**Protein Degradation:**
- Cellular proteins undergo a constant turnover, with damaged, misfolded, or no longer needed proteins being targeted for degradation.
- The primary pathway for protein degradation is the ubiquitin-proteasome system (UPS).
- The UPS involves tagging proteins with ubiquitin, a small protein, which marks them for degradation by the proteasome.
- The proteasome is a large, multi-subunit complex that unfolds and degrades ubiquitinated proteins into short peptides.

**Regulation of Protein Stability:**
- **Ubiquitination:** The process of attaching ubiquitin to a protein is tightly regulated, controlling its stability. E3 ubiquitin ligases specifically target proteins for ubiquitination.
- **Deubiquitination:** Deubiquitinases remove ubiquitin from proteins, stabilizing them and preventing their degradation.
- **Post-translational modifications (PTMs):** Modifications like phosphorylation, acetylation, and glycosylation can influence protein stability. PTMs can either target proteins for degradation or protect them.
- **Chaperone proteins:** Chaperones play a crucial role in maintaining protein stability by assisting in folding and preventing aggregation.
- **Stress response:** Cellular stress, such as heat shock or oxidative stress, can trigger mechanisms to stabilize essential proteins and degrade damaged ones.

**Factors Affecting Protein Stability:**
- **Protein sequence:** The amino acid sequence determines the protein's inherent stability.
- **Environmental factors:** Temperature, pH, and the presence of cofactors can affect protein stability.
- **Cellular conditions:** Cellular processes, including metabolism and signaling pathways, influence protein stability.

**Significance of Protein Stability Regulation:**
- **Cellular homeostasis:** Maintaining protein stability is essential for normal cellular function and survival.
- **Disease pathogenesis:** Dysregulation of protein stability is implicated in various diseases, including cancer and neurodegenerative disorders.
- **Drug development:** Targeting protein stability is a promising approach for drug development, particularly for diseases related to protein misfolding or degradation.
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Proteins (23)

Compounds (2,223)