Post-translational Modifications: What They Are And How They Are Associated With The Disease
Proteins are the macromolecules of life. They represent 80% of the dehydrated protoplasm of the entire cell and form around 50% of the dry weight of all our tissues, so growth, biosynthesis and tissue repair depend completely on them.
The amino acid is the basic unit of the protein, because through consecutive peptide bonds, these molecules give rise to the protein chains that we know from biology lessons. Amino acids are composed of carbon (C), oxygen (O), nitrogen (N) and Hydrogen (H), 4 of the 5 bioelements that make up 96% of the Earth’s cell mass. To give you an idea, we have 550 gigatons of organic carbon on the planet, 80% of which comes from the plant matter that surrounds us.
The process of protein synthesis within the cell is a complex dance between DNA, RNA, enzymes, and assembly chains. In this opportunity, We give you a general overview of protein formation at the cellular level, with special emphasis on post-translational modifications
First of all, we must lay certain foundations. The human being has its genetic information within the nucleus (not counting the mitochondrial DNA), and it has protein or RNA coding sequences, called genes. Thanks to the Human Genome Project, we know that our species has about 20,000-25,000 coding genes, which only represents 1.5% of the total DNA in our body
DNA is made up of nucleotides, which are of 4 types, depending on the nitrogenous base they present: adenine (A), guanine (G), cytosine (C) and thymine (T). Each amino acid is encoded by a triplet of nucleotides, which are known as “codons.” We give you the example of a few triplets:
All of these triplets or codons code for the amino acid alanine, interchangeably In any case, these do not come directly from genes, but are segments of RNA, which are obtained from the transcription of nuclear DNA. If you know genetics, you will have noticed that one of the codons has uracil (U), the analogue of thymine (T) in RNA.
So that, During transcription, a messenger RNA is formed from the information present in the genes and it travels outside the nucleus, to the ribosomes, which are located in the cytoplasm of the cell Here, the ribosomes “read” the different codons and “translate” them into chains of amino acids, which are carried one by one by the transfer RNA. We give you one more example:
GCU-UUU-UCA-CGU
Each of these 4 codons code, respectively, for the amino acids alanine, phenylalanine, serine and arginine. This theoretical example would be a tetrapeptide (oligopeptide), since to be a normal protein, it must contain at least 100 of these amino acids. In any case, this explanation generally covers the transcription and translation processes that give rise to proteins within cells.
What are post-translational modifications?
Post-translational modifications (PTM) refer to the chemical changes that proteins undergo once they have been synthesized on ribosomes Transcription and translation give rise to propeptides, which must be modified so that, ultimately, the real functionality of the protein agent is achieved. These changes can take place through enzymatic or non-enzymatic mechanisms.
One of the most common post-translational modifications is the addition of a functional group. In the following list, we give you some examples of this biochemical event.
There are many more mechanisms for adding functional groups, since nitrosylation, glycosylation, glycation or prenylation have also been recorded From the formation of drugs to the synthesis of biological tissues, all of these processes are essential for the survival of our species, in one way or another.
As we have said previously, the human genome contains 25,000 genes, but the proteome of our species (the total proteins expressed in a cell) is around one million protein units. In addition to messenger RNA splicing, post-translational modifications are the basis of protein diversity in humans since they are capable of adding small molecules through covalent bonds that completely change the functionality of the polypeptide.
In addition to the addition of specific groups, there are also modifications that link proteins together. An example of this is sumoylation, which adds a miniature protein (small ubiquitin-related modifier, SUMO) to target proteins. Protein degradation and nuclear localization are some of the effects that this process has.
Another important additive post-translational mechanism is ubiquitination, which, as its name indicates, adds ubiquitin to the target protein. One of the multiple functions of this process is to direct protein recycling, since ubiquitin binds to polypeptides that must be destroyed.
Today, About 200 different post-translational modifications have been detected , which affect many aspects of cellular functionality, including mechanisms such as metabolism, signal transduction and protein stability itself. More than 60% of the protein sections resulting from post-translational modifications are associated with the area of the protein that interacts directly with other molecules, or in other words, its active center.
Post-translational modifications and pathological conditions
Knowledge of these mechanisms is already a treasure for society, but things get even more interesting when we discover that post-translational modifications are also useful in the medical field.
Proteins that have the CAAX sequence inside them, cysteine (C) – aliphatic residue (A) – aliphatic residue (A) – any amino acid (X), are part of many molecules with nuclear sheets, are essential in various regulatory processes and In addition, they are also present on the surface of cytoplasmic membranes (the barrier that delimits the inside of the cell from the outside). The CAAX sequence has historically been associated with the development of diseases, since it governs the post-translational modifications of the proteins that present it
As indicated by the European Commission in the article CAAX Protein Processing in Human DIsease: From Cancer to Progeria, today efforts are being made to use enzymes that process proteins with the sequence as therapeutic targets for cancer and progeria. CAAX. The results are too complex at the molecular level to be described in this space, but the fact that they are trying to use post-translational modifications as an object of study in diseases highlights their clear importance.
Summary
Of all the data presented in these lines, we want to highlight one of special importance: Human beings have about 25,000 different genes in our genome, but the cellular proteome amounts to a million proteins This figure is possible thanks to post-translational modifications, which add functional groups and link proteins together, in order to give specificity to the macromolecule.
If we want you to stay with a central idea, this is the following: DNA is transcribed into messenger RNA, which travels from the nucleus to the cell cytoplasm. Here, this is translated into the protein (which houses its instructions in the form of codons), with the help of transfer RNA and ribosomes. After this complex process, post-translational modifications take place, in order to give the protopeptide its definitive functionality.
