6.8: Kovalent gebunden Protein-Regulatoren

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.

These groups modify specific amino acids in a protein. Phosphate groups can only be covalently attached to the amino acids serine, threonine, and tyrosine, whereas methyl and acetyl groups can only be linked to lysine.  These groups are added to and removed from a protein by an enzyme or pair of enzymes.    For example, an acetyltransferase adds an acetyl group to a protein, and a deacetylase can remove it. Each of these modifiers can have different effects on the protein to which it is attached depending on the number and location of the modifications. When a single ubiquitin molecule is covalently linked to a certain cell surface receptor, this protein is targeted for endocytosis; on the other hand, when multiple ubiquitins linked together are attached to this protein, it is marked as a target for proteolytic degradation.

A single protein can undergo multiple modifications simultaneously to control its function. One well-known example of a protein regulated by multiple covalent modifications is the tumor-suppressor protein, p53.  p53 undergoes a variety of modifications in response to various types of stress, including radiation and carcinogens. Some modifications include phosphorylation, acetylation, and sumoylation in response to UV and gamma radiations. The sites and types of modifications can vary depending on the stressor. Studies have shown that UV and gamma radiation can result in the phosphorylation of serine 33, but serine 392 can be phosphorylated when exposed to UV but not gamma radiation. Other kinds of stress, such as exposure to hypoxia, anti‐metabolites, and actinomycin D, can result in the acetylation of p53. The modifications can also vary between different cell types and organisms.

Viele Proteine werden durch kovalent verknüpfte Moleküle reguliert, darunter funktionelle Gruppen wie Methyl- oder Acetyleinheiten und kleine Proteine wie Ubiquitin.

Kovalente Bindungen treten an spezifischen Aminosäuren in der Polypeptidkette auf. Zum Beispiel sind Phosphatgruppen kovalent an Serin, Threonin oder Tyrosin gebunden; Methyl- und Acetylgruppen sind an Lysin gebunden; und Ubiquitin ist mit Lysin-, Cystein-, Serin- oder Threoninresten verbunden.

Ein Enzym oder ein Paar von Enzymen katalysiert reversibel diese posttranslationalen Modifikationen. Eine Acetyltransferase kann ein Protein acetylieren, während eine Deacetylase die Gruppe später entfernen kann.

Diese Modifikationen können die Funktion oder die Lokalisation eines Proteins in einer Zelle verändern.

Zum Beispiel reguliert die Acetylierung von Histonproteinen die Genexpression, indem sie die DNA-Struktur öffnet, um die Gentranskription zu aktivieren. Andererseits ist bekannt, dass die Methylierung von Histonproteinen die Transkription unterdrückt, indem sie die Struktur strafft.

Ein weiteres Beispiel ist p53, ein Multidomänen-Tumorsuppressorprotein, das als Reaktion auf Stress mehrere kovalente Modifikationen durchläuft. Die Exposition gegenüber DNA-schädigenden Stoffen wie UV- und Gammastrahlung kann zu einer Phosphorylierung des Proteins führen.

Die Phosphorylierung verbessert die Stabilität und aktiviert p53, wodurch es an die durch die Strahlung geschädigte DNA bindet und Zellen mit mutierter DNA sich unkontrolliert teilen.

Zusätzlich zur Phosphorylierung ermöglichen verschiedene Arten von Modifikationen, die an einem einzelnen Proteinmolekül auftreten, wie z. B. p53, die genaue Kontrolle seiner Funktionen wie Zellzyklusarrest, DNA-Reparatur und Apoptose einer Zelle.

• Post-Translational Modification - Covalent modifications made to proteins after synthesis.
• Covalently Linked Proteins - Proteins that have been chemically bonded together.
• Protein Degradation - The process by which proteins are broken down in cells.
• Covalent Regulation - Control of protein function by adding/removing chemical groups.
• Ubiquitination - A post-translational modification involving the attachment of ubiquitin to proteins.

• Define Post-Translational Modification - The changes made to proteins after they are synthesized (e.g., covalently linked).
• Contrast Pre and Post-Translational Modification - Understand the differences and unique functions (e.g., covalent regulation vs ubiquitination).
• Explore Examples - How proteins are targeted for degradation (e.g., ubiquitination).
• Explain the Process - How post-translational modifications regulate protein functions.
• Apply in Context - How post-translational modifications impact biological systems.

• What is Post-Translational Modification and why is it important?
• What are the different types of Post-Translational Modifications?
• How does Post-Translational Modification regulate protein function?

• Students - Grasp the complex nature of protein structure and function.
• Educators - Provides a detailed overview of an advanced topic in molecular biology.
• Researchers - Essential understanding for genetic research and drug discovery efforts.
• Science Enthusiasts - Delve into the intricacies of protein regulation and modification.