An Overview of Post-Translational Configurations in Proteins

This article describes very shortly how natural mechanisms operate to prevent genes from becoming rigid in their expression.

The following headings are covered:

  • A brief overview of post-translational protein modification (PTM)
  • Mechanisms of post-translational modification
  • The most commonly seen post-translational modifications
  • The effect of post-translational modification in illness and health

A Brief Overview of Post-Translational Protein Modification

Cells are living structures that need to detect and to respond in appropriate ways to environmental changes. This holds good for both internal and external changes. One of the ways in which such a response occurs is by chemical alteration of proteins. These are called reversible PTMS and signal the occurrence of conditional changes in the chemical structure from sensor to effector cells.

These PTMs are very important when it comes to shifting the final protein end product of gene expression, and also plays a part in many physiological and pathological processes in living organisms, as well as being essential to a number of cell processes including  cell differentiation (when a cell undergoes maturational changes),  breakdown of proteins, cell signaling and regulation, control of gene expression, and interactions between proteins.

Mechanism of Post-Translational Modification

PTMs may be observed during any stage of the lifecycle of the protein. In some cases the modification follows translation, in order to allow the protein to undergo folding correctly, or to guide it into the right location in the cell, such as on the membrane or in the nucleus.

Other proteins are modified after folding has been completed and they have reached their cellular stations, and in this case the modification is meant to switch catalytic activity on or off. Sometimes a protein is covalently bonded to a specific group which marks it out for breakdown.

The modification of a protein is typically carried out through a mixture of cleavage of the translated protein and the linkage of the protein with functional groups, which take the protein through several steps in which the protein matures or is activated.

PTMs are found to take place at specific amino acid side chains or peptide linkages, most often via enzymes. There are more than 200 types of PTM which are mediated by enzymes, which therefore take up 5% of the proteome. Such enzymes are varied in function, being phosphatases, kinases, ligases and transferases.

These are concerned with linking or delinking several types of functional groups or lipids, or sugars, or other proteins, to protein side chains composed of amino acids. Another group of enzymes is the protease family which disrupts peptide bonds to remove certain sequences, or subunits which play a regulatory role.

Some proteins are capable of auto-modification as they have domains with autocatalytic activity, these being called autokinase and autoproteolytic domains. Some PTMs can be reversibly performed, as with phosphatase-mediated hydrolysis of the phosphate group to remove it from the protein and thus reverse the biological activity of the group. This is shown in Figure 1.

Types of post-translational modifications (PTMs)

Figure 1. Types of post-translational modifications (PTMs)

The Most Commonly Seen Post-Translational Modification

Figure 2 shows the phosphorylation of a protein, which is the type of PTM about which most is known. About a third of all proteins in mammals undergo phosphorylation, on a rough estimate, which is important in the modulation of the function of these proteins.

Mass spectrometry methods have advanced so far as to help thousands of sites of PTM to be identified. This has resulted in the emergence of new strategies for enrichment, which in turn has led to the discovery of the universal importance to the cell of several PTMs like acetylation, ubiquitylation, O-GlNac, and N-linked glycosylation. More than 200 different PTMs are known at present, some of which involve small modifications by chemical linkages of phosphate or acetyl groups, and others which involve the linkage of whole proteins such as ubiquitylation, seen in Figure 3.

WB result of phospho-Marcks antibody (10018-3-AP, 1:1500) with mouse J774 macrophage cells treated with PMA.

Figure 2. WB result of phospho-Marcks antibody (10018-3-AP, 1:1500) with mouse J774 macrophage cells treated with PMA.

MDA-MB-453s cells were subjected to SDS PAGE followed by western bolt with 10201-2-AP (ubiquitin Antibody) at a dilution of 1:600.

Figure 3. MDA-MB-453s cells were subjected to SDS PAGE followed by western bolt with 10201-2-AP (ubiquitin Antibody) at a dilution of 1:600.

The Effect of Post-Translational Modification in Illness and Health

In many chronic medical conditions such as diabetes, heart disease, cancer and neurological degenerative disorders, protein and PTM analysis becomes important. Specific methods for detection and purification of proteins which have undergone PTM become necessary. Such techniques are being evolved and tuned in proteomics, helping to surmount these challenges.

References

  1. Chemical biology: dressed-up proteins.
  2. Concepts in sumoylation: a decade on.
  3. Proteomic analysis in the neurosciences.
  4. The Roles of Post-translational Modifications in the Context of Protein Interaction Networks
  5. Deciphering a global network of functionally associated post-translational modifications.
  6. PTMcode: a database of known and predicted functional associations between post-translational modifications in proteins.
  7. Citrullination: a posttranslational modification in health and disease.

About Proteintech Group, IncProteintech Group, Inc

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Last updated: Sep 28, 2018 at 4:45 AM

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