4.9:

4.9: リン酸化

Phosphorylation

JoVE Core
Molecular Biology

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JoVE Core Molecular Biology

Phosphorylation

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4.8: Cooperative Allosteric Transitions

4.10: Protein Kinases and Phosphatases

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01:02 min

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November 23, 2020

Overview

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.

During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly phosphorylated amino acids. Accordingly, protein kinases are classified as serine/threonine kinases, tyrosine kinases, or dual action kinases if they can phosphorylate all three amino acids. Conversely, protein phosphatases catalyze the removal of the phosphate group (dephosphorylation), restoring the original properties of the protein.

Under physiological conditions, phosphorylation and dephosphorylation are tightly regulated to prevent prolonged changes in protein structure and function. Disruption of this balance can cause diseases, including cancer and various neurodegenerative disorders. For instance, a protein called tau is hyperphosphorylated in Alzheimer’s disease (AD). Physiologically, tau regulates the shape, structure, and development of neurons. The tau protein contains over 80 serine, threonine, and tyrosine residues, of which only a fraction is usually phosphorylated. In the brains of patients with AD, tau is abnormally and excessively phosphorylated. This alters the solubility of the protein, forming toxic insoluble aggregates that lead to neuronal death.

Transcript

Phosphorylation, the addition of a phosphate group, is an important chemical modification that helps cells to regulate protein function.

During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of a target protein.

As a result, the target protein may change conformation, or the phosphorylated region can act as a novel binding site for other proteins.

These changes can modify the function of a protein, completely activating or deactivating it.

The phosphate group can be removed by the action of protein phosphatases, enzymes that catalyze the dephosphorylation of proteins.

In this way, kinases and phosphatases can reversibly regulate the activity of certain proteins turning them on or off as and when required by the cell.

Key Terms and definitions

Phosphorylation - The process of adding a phosphate group to a molecule using enzymes.
Kinase - An enzyme that catalyzes the transfer of a phosphate group from ATP to a specific molecule.
Phosphatase - An enzyme that removes a phosphate group from a molecule.
Phosphorylated Amino Acid - Amino acid that has had a phosphate group attached to it.
Phosphate Group - A group consisting of a phosphorus atom covalently bound to four oxygen atoms.

Learning Objectives

Define Phosphorylation – Understand the process of adding a phosphate group to a protein (e.g., phosphorilation).
Contrast Kinase vs Phosphatase – Understand the different actions they play on molecules (e.g., kinase vs phosphatase).
Explore the Effects on Proteins – Consider impacts of the addition/removal of phosphate groups (e.g., amino acid phosphorylation).
Explain Role of Phosphorylation in Biochemical Process - Discuss its importance.
Apply Phosphorylation in Cellular Context – Consider its crucial role in cell functioning.

Questions that this video will help you answer

What is phosphorylation and why is it important?
What's the difference between kinase and phosphatase?
How does phosphorylation affect protein function?

This video is also useful for

Biology Students – Grasp how phosphorylation and associated terms impact biological processes.
Biochemistry Educators – Clear terminology and concepts for teaching about protein functioning.
Cell Biology Researchers – Relevance for studying cell signaling and function.
Molecular Biology Enthusiasts – Insight into crucial biochemical processes.

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