Posttranslational modifications – What are these things stuck to my protein?

If you took introductory biochemistry, you are probably familiar with the most common biopolymers: nucleic acids (DNA & RNA), proteins, and carbohydrates. The roles of the first two polymers are probably best encapsulated in what is known as the central dogma of molecular biology (coined by Prof. Crick).

Essentially, DNA stores the sequential coding information, it is transcribed into RNA which delivers specific fragments (as mRNA) which become translated into protein sequences. The proteins tend to be the functional molecules in the cell which catalyze chemical change or form essential structures in the cell (and generate the phenotype of the cell/organism). So what happens after translation (posttranslation, and the namesake of this blog)?

Posttranslational modifications (PTM) are chemical changes that happen to proteins after the coding sequence has been converted into a protein. By defenition, these changes are not encoded directly by genetic information. There are many examples, with glycosylation (attachment of a carbohydrate) and phosphorylation (attachment of a phosphate) being some of the more prevalent examples (here is an excellent review on the subject).

So, what do these modifications do? (The real answer is a long one – so I’ll just include some highlights.) A lot of these modifications change the function of the protein. As an example, some sulfotransferase enzymes are inactive as their primary sequence, but when the active site residues are modified (by an enzyme known as FGE) the enzyme becomes active. Some modifications actually control which proteins interact with each other, a mechanism that is essential in immune cell response (among many others.) PTM can also change the stability, shape, or flexibility of proteins.

One of the problems in this field is that PTM, since they aren’t directly encoded, aren’t easy to predict (i.e. things get messy). Think of it this way: if the genetic information stored in DNA is the blueprint of a house, PTM end up being the tweaks and changes that our builder might include that we didn’t specifically ask for (but might even be needed to make things work). This one feature, which leads to complexity and variability, is a large part of why we know a lot less about PTM than we do about, say, DNA. As a result, to study these modifications we have to go in and specifically see what modifications took place in a given cell or condition.

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