May 30: the process of our cells to transform genes into useful proteins works in a very similar way to the badembly line of a car factory; There are schemes, parts, workers, engines, quality control systems and even recycling equipment. If the recycling process of the cell fails, abnormal protein fragments accumulate, which could cause the death of the cell. In nerve cells, the process is linked to a variety of neurodegenerative diseases, such as ALS and dementia.
A new study from the laboratory of Claudio Joazeiro, Ph.D., published online in the journal. Cell On May 30, discover how the simplest organisms, bacteria and archaea, manage the recycling of incomplete proteins. The findings not only provide new directions to combat the virulence of some of the most dangerous pathogens of humanity, such as listeria, staphylococcus and streptococcus, also have implications for our understanding of how life evolved.
Joazeiro's group found that the mechanism is not so different from that previously discovered in plant, animal and fungal cells.
"We know that as the cells produce proteins, this process is occasionally stops due to errors," says Juazeiro, who holds joint appointments in the Research Department of Molecular Medicine at Scripps in Jupiter, Florida, and at the Center for Molecular Biology from the University of Heidelberg. in Germany.
"One of the problems with this is that the accumulation of partially formed proteins can be toxic, so in our laboratory, we wonder how the cells perceive this and how they disbademble these proteins and recycle the building blocks."
Organelles called ribosomes serve as motors for badembling proteins within cells. If they stagnate during the process of badembling the parts (amino acids), the cells have a variety of systems to respond to. In human cells and other eukaryotic cells, when a ribosome is clogged, the rescue factors are divided. A protein called Rqc2, also known as NEMF, targets and recruits another protein, the ubiquitin ligase Ltn1, also called listerine. Joazeiro's laboratory previously discovered that Ltn1 marks the truncated protein fragment in ribosomes with a destruction tag called ubiquitin. The protease saws then takes care of the demolition.
By underlining the importance of this recycling process, Joazeiro discovered in 2009 that mutations in Ltn1 can cause the death of nerve cells in mice, which results in symptoms similar to ALS. Bacteria have related, but somewhat more direct systems to treat the arrested ribosomes and their protein fragments, according to the Cell report. When studying the bacterium B. subtilis, Joazeiro's team discovered that Rqc2 marks the protein fragment with a flag, a polymer made from the amino acid alanine. Thus marked, the proteases come to cut the bad fragment.
Previous studies had suggested that in some pathogenic bacteria, the Rqc2 proteins had a different job, one that worked outside the cell, which helped bind the microbes to the hosts.
"We have discovered that this is not the whole story," says Joazeiro. "Rqc2 plays a more fundamental role within bacterial cells."
The next step will be to find out whether the defective virulence of streptococcal strains lacking Rqc2 is primarily a consequence of their inability to recycle protein fragments within the cell. As increasing varieties of pathogens develop resistance to the antibiotics of multiple drugs, understanding bacterial virulence may be especially necessary.
Equally important to Juazeiro is the realization that Rqc2 serves as a "living" molecular fossil, illuminating new insights into the ancient ancestral organism that emerged about 4 billion years ago to form the very base of the tree of life that became in the biodiversity of the current planet. .
"Shortly after the cells invented the way to produce proteins, they were also confronted with the determination of how to deal with proteins incompletely," says Joazeiro. "The badyzes suggest that a homologue of Rqc2 in the last universal common ancestor has already performed this task."
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