Mutant proteins can indicate the weak points of a cancerous tumor
It is known that point replacements of amino acid residues in proteins, which occur due to DNA mutation, can provoke a change in their functions in cells. Scientists believe that such transformations play a key role in the development of cancer. The study of mutant proteins undertaken by Russian scientists from MIPT, the Institute of Biomedical Chemistry, the Institute of Energy Problems of Chemical Physics of the Russian Academy of Sciences and the FNCC of Physico-Chemical Medicine – they compiled an algorithm for searching for mutant proteins in living cells by mass spectrometric analysis - can help identify the vulnerabilities of cancer cells and develop more effective drugs against cancer in the future. The results of the work are published in the journal Proteomics (Lobas et al., Exome-based proteogenomics of HEK-293 human cell line: Coding genomic variants identified at the level of shotgun proteome).
Proteogenomics – the field to which the new research relates, combines the methods of genomics and proteomics (the science that studies the totality of proteins of a cell or an entire organism). It uses databases on the sequences of amino acids found specifically in the studied cells. The method of mass spectrometry allows to determine the exact weight of protein molecules, peptides and their parts in the available samples.
Russian scientists have created an algorithm that can compare the mass spectrometric results of different research groups and find protein mutations associated with the malignant process. They tested their development on the example of the HEK-293 cell line taken from the kidney of a human embryo. Such a culture is often used in scientific research as a model of human cells, since it is quite easy to grow in laboratories. But in addition, the HEK-293 line contains many mutations and that is why it can serve as an excellent model for testing a proteogenomic approach to cancer research.
For the experiment, the researchers prepared an expanded database based on the results of sequencing of the exome (a set of gene sections encoding the sequence of amino acids in a protein) of the HEK-293 cell line. The "decoding" of the exome helped to focus the attention of scientists only on protein-coding genes and to identify the location of exons in them. As a result, the research base increased by 1,336 variants of sequences. In other words, sequences that differ from the original ones by only one or several amino acids have been added to the protein "dictionary". Without such a detailed database, the search program could not effectively find partially "wrong" proteins.
It is known that mutations constantly occur in every living cell, and especially often in malignant cells. Thus, the detection of proteins that differ from the "right" ones will help scientists understand how a cancer cell differs from a normal one.
Figure from the MIPT press release Peptide mutants help identify vulnerability in tumor cells - VM
"Our approach can be further used to search for cancer-associated mutations based on proteomic data. This, in turn, will help in the study of the protein composition of tumors and the development of drugs "aimed" at mutant proteins produced in tumor cells," said Mikhail Gorshkov, head of the Laboratory of Physico–chemical methods for studying the structure of substances of the INEPCF RAS, one of the authors of the work.
Portal "Eternal youth" http://vechnayamolodost.ru
01.09.2016