Post Translational Modification

Beyond what genes can express

While most recent estimates of the human genome’s size fall between 20,000 and 25,000 genes, that number is dwarfed by the human proteome our genome encodes, which comprises more than 1 million proteins.

Single genes are responsible for the synthesis of multiple proteins, and one way this is accomplished is through the process of post-translational modification (PTM).

Protein PTMs have been shown to play a key role in cellular processes such as differentiation, and regulation of gene expression.

PTMs expand the range of gene products possible via the chemical addition or subtraction of functional groups to proteins already synthesized from an mRNA template without instructions for such alterations. These modifications play critical roles in the regulation of a protein’s activity and type of interaction with other molecules such as lipids, nucleic acids, enzymatic cofactors and other proteins.

Types of post-translational modification

Some of the most common and important PTMs so far identified include:

• Phosphorylation — The addition of a phosphate group to tyrosine, serine or threonine amino acid residues; accomplished by kinase enzymes; one of the most important and well-studied PTMs that occur within all organisms
• Methylation — The addition of a methyl group, via methyltransferase enzyme, to an arginine or lysine residue; methylation of histone (a DNA packaging protein) can either activate or repress genes depending on the amino acid modified
• Acetylation — The addition of an acetyl group to a protein; gene regulation is largely mediated by histone acetylation and deacetylation; acetylation of the p53 gene is essential to its tumor-suppressing activity
• Glycosylation — The addition of a glycan oligosaccharide to asparagine, serine or threonine residues; involved in antigen recognition and inflammatory response
• Ubiquitination — The addition of ubiquitin protein to a lysine residue, either singly (monoubiquitination) or in a chain (polyubiquitination); proteins modified in the latter fashion are tagged for degradation
• Lipidation — The addition of a lipid group to a cysteine or glycine residue; involved in biological regulation, membrane association and apoptosis (programmed cell death)
• Proteolysis — The splitting of proteins into constituent polypeptides or amino acids; removing an N-terminal methionine residue, for example, can activate an inactive protein

Phosphorylation: adding a phosphate to 1 of a protein’s amino acid side chains. Phosphate groups carry 2 negative charges, and their addition to a protein results in a conformational change of the protein’s structure.

References