Researchers at the University of Murcia have discovered the gene corresponding to an enzyme that was considered ‘orphan’ for not knowing its origin or its function. The protein is involved in diseases such as cancer or Alzheimer’s.
For 50 years, scientists have been looking for the identity of an enzyme called TMEM189, which was classified as ‘orphan’ because its gene that gave it origin and function was unknown. Now, a team of researchers from the University of Murcia (UMU) has revealed the gene and its function within the cell thanks to a bacterium. Details are published in the journal Science.
The UMU team has been working with Myxococcus xanthus, a bacterium that lives in the soil for years. According to the principal investigator, the effort to discover the role of a gene (called carF) that the bacteria uses to perceive light, led them to identify the human gene.
“Analyzing possible human proteins we discovered that there was a protein, of unknown function, that was very similar to the CarF protein of the bacteria and, therefore, we wondered if the human protein worked in the same way as the bacterial one,” says Elías Arnanz .
Present in the human brain and heart
To answer this question, the researchers replaced the bacterial gene with its equivalent gene in humans. “We discovered that the protein of humans and that of bacteria work identically, despite the enormous evolutionary distance between the two organisms,” concludes Elías.
In this way, the team determined that the ‘orphan enzyme’ was involved in the manufacture of plasminogens, a class of phospholipids found in cell membranes, especially in the brain and in the heart.
In common diseases, such as cancer or Alzheimer’s disease, or other rare diseases, such as Zellweger’s syndrome (cerebro-hepato-renal syndrome) or rhizomelic chondrodysplasia punctate, there are considerable changes in plasminogen levels.
In the case of Alzheimer’s, for example, a very significant reduction is observed in the affected areas of the brain. “In some cancers such as gastrointestinal there is an increase in these compounds and in others a decrease,” explains the principal investigator of this study, Montserrat Elías and points out that for this reason it has been considered to use plasminogens as early markers of cancer.
The contributions of these UMU experts will allow exploring the direct relationship of plasminogens with various pathologies and, in addition, to reveal a very novel function of plasminogen: to allow a bacterium to see the light. In addition, the equivalence between the two proteins will allow analyzing quickly, in the bacterium, the possible effect of the changes that are found in the human gene.