Related Experiment Video
Updated: Jul 19, 2025
09:54
Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area
Published on: August 10, 2012
25.8K
An Inherent Difference between Serine and Threonine Phosphorylation: Phosphothreonine Strongly Prefers a Highly
Anil K Pandey1, Himal K Ganguly1, Sudipta Kumar Sinha1,2
1Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States.
ACS Chemical Biology
|August 18, 2023
Summary
Phosphorylation of serine and threonine residues in proteins causes significant structural changes. Threonine phosphorylation, in particular, induces a strong disorder-to-order transition, mimicking proline
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- Protein phosphorylation by kinases and phosphatases regulates cellular functions.
- Understanding the structural impact of phosphorylation is crucial for cellular signaling.
- Serine and threonine phosphorylation are key post-translational modifications.
Purpose of the Study:
- To investigate the structural consequences of serine and threonine phosphorylation.
- To elucidate the conformational changes induced by phosphorylation in peptides and proteins.
- To provide a structural basis for the differential roles of serine and threonine phosphorylation.
Main Methods:
- Circular dichroism spectroscopy
- Nuclear Magnetic Resonance (NMR) spectroscopy
- Bioinformatic analysis of the Protein Data Bank (PDB)
- Small-molecule X-ray crystallography
- Computational investigations
Main Results:
- Phosphorylation of serine and threonine residues induces significant conformational restriction in their dianionic forms.
- Dianionic phosphothreonine adopts a cyclic conformation with restricted ϕ angles (∼-60°), stabilized by noncovalent interactions.
- This phosphothreonine structural signature, mimicking proline's backbone cyclization, is observed in various proteins, including kinase activation loops.
- Serine phosphorylation typically causes smaller, rheostat-like changes, while threonine phosphorylation induces larger, step-function-like switches.
Conclusions:
- Phosphorylation significantly alters protein structure and dynamics.
- Phosphothreonine's unique conformational preference offers a distinct regulatory mechanism compared to phosphoserine.
- These findings explain the differential evolution and utilization of serine and threonine phosphorylation sites in proteins.
More Related Videos
Related Concept Videos
01:02Phosphorylation
50.5K
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...
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...
50.5K
02:54Protein Kinases and Phosphatases
13.2K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.2K
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.5K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.5K
01:48ATP Synthase: Mechanism
14.8K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.8K
01:22Amplifying Signals via Enzymatic Cascade
8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K
01:31ATP Energy Storage and Release
10.1K
ATP is a highly unstable molecule. Unless quickly used to perform work, ATP spontaneously dissociates into ADP and inorganic phosphate (Pi), and the free energy released during this process is lost as heat. The energy released by ATP hydrolysis is used to perform work inside the cell and depends on a strategy called energy coupling. Cells couple the exergonic reaction of ATP hydrolysis with endergonic reactions, allowing them to proceed.
One example of energy coupling using ATP involves a...
One example of energy coupling using ATP involves a...
10.1K