Getting a chemical handle on protein post-translational modification.
William P Heal1, Edward W Tate
1Department of Chemistry and Chemical Biology Centre, South Kensington Campus, Imperial College, London, UKSW7 2AZ.
Organic & Biomolecular Chemistry
|February 6, 2010
Summary
Chemical proteomics uses bioorthogonal chemistry to tag protein modifications, advancing cell and systems biology. This technology helps identify complex chemical changes in proteins, crucial for understanding biological functions.
Area of Science:
- Biochemistry
- Proteomics
- Chemical Biology
Background:
- The proteome exhibits significant chemical complexity due to post- and co-translational protein modifications.
- Identifying and characterizing these modifications in complex biological samples is a major challenge in post-genomic research.
Purpose of the Study:
- To highlight chemical proteomics as a key technology for studying protein modifications.
- To explain how chemical proteomics addresses the challenge of identifying complex protein modifications.
Main Methods:
- Utilizing protein-modifying enzymes to selectively target modified amino acid residues.
- Employing bioorthogonal chemoselective elaboration to attach chemical tags to specific modifications.
- Leveraging these chemical tags for the detection and characterization of protein modifications.
Main Results:
- Demonstrates the power of chemical proteomics in navigating proteomic complexity.
- Enables the identification and characterization of specific protein modifications within complex mixtures.
- Advances the understanding of the functional implications of protein modifications.
Conclusions:
- Chemical proteomics offers powerful tools for dissecting the chemical landscape of proteins.
- This approach is vital for functional studies in cell and systems biology.
- It opens new avenues for understanding the roles of protein modifications in biological systems.
Related Concept Videos
02:04Covalently Linked Protein Regulators
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.
These groups modify specific amino acids in a protein.
02:04Covalently Linked Protein Regulators
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.
These groups modify specific amino acids in a protein.
01:26Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
01:02Phosphorylation
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...
02:54Protein Kinases and Phosphatases
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...
01:25Protein Glycosylation
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...