Researchers do not know how all the proteins and enzymes in the human body function, far from it. Now they have come a bit closer to understanding how an enzyme that appears to be important to cancer development behaves inside the cells.

The new study that has just been published in the scientific journal Nature Communications shows first of all that the enzyme methyltransferase (MTase)-like protein 13 (METTL13) helps control the formation of new proteins in the cells.

'Mistakes in the production of proteins are undesirable, as we know from other studies that it can result in the development of cancer tumors and degenerative brain disorders like Alzheimer's and Parkinson's. Therefore, the new knowledge of how this enzyme functions is significant', says the senior researcher.

The enzyme helps control protein synthesis by placing so-called methyl marks on a particular protein called eEF1A. Eukaryotic elongation factor 1 alpha (eEF1A) delivers aminoacyl-tRNA to the ribosome and thereby plays a key role in protein synthesis. 

Human METTL13 contains two distinct MTase domains targeting the N terminus and Lys55 of eEF1A, respectively. The biochemical and structural analyses provide detailed mechanistic insights into recognition of the eEF1A N terminus by METTL13. Through ribosome profiling, authors demonstrate that loss of METTL13 function alters translation dynamics and results in changed translation rates of specific codons.

'If methyl is not attached correctly to the protein it will not be able to do its job properly. And that again affects the formation of proteins in the cell, which will take place at a suboptimal pace, and even though that may not sound so bad, it appears to be connected with very serious disorders', says the lead author.

The researchers have shown how the enzyme functions by studying isolated human cancer cells using advanced mass spectrometers which, in short, are able to identify and quantify proteins and their methyl-modifications in a cell.

Now the researchers hope the study will lead to the development of methods and drugs able to target and assure the enzyme to function as intended in our cells.

https://healthsciences.ku.dk/news/2018/09/researchers-uncover-previously-unstudied-cancer-enzyme/

https://www.nature.com/articles/s41467-018-05646-y