Amazing stuff! Good news!
"Much like humans generate mountains of garbage, our cells are constantly discarding proteins that are damaged or no longer needed. The cellular waste disposal system called the proteasome is best known for its central role in protein degradation and recycling, but as far back as the 1990s it was shown that products of this process – short protein sequences called peptides – can be displayed on the cell surfaces, helping the immune system to identify threats.
In a new study ... reports uncovering a surprising immune mechanism involving the proteasome. The team discovered that some of the peptides released in the proteasome during protein breakdown are capable of killing bacteria. These findings expand our understanding of the body’s innate defenses and offer new hope for tackling the growing threat of antibiotic resistance. ..."
From the abstract:
"For decades, antigen presentation on major histocompatibility complex class I for T cell-mediated immunity has been considered the primary function of proteasome-derived peptides. However, whether the products of proteasomal degradation play additional parts in mounting immune responses remains unknown.
Antimicrobial peptides serve as a first line of defence against invading pathogens before the adaptive immune system responds. Although the protective function of antimicrobial peptides across numerous tissues is well established, the cellular mechanisms underlying their generation are not fully understood.
Here we uncover a role for proteasomes in the constitutive and bacterial-induced generation of defence peptides that impede bacterial growth both in vitro and in vivo by disrupting bacterial membranes.
In silico prediction of proteome-wide proteasomal cleavage identified hundreds of thousands of potential proteasome-derived defence peptides with cationic properties that may be generated en route to degradation to act as a first line of defence.
Furthermore, bacterial infection induces changes in proteasome composition and function, including PSME3 recruitment and increased tryptic-like cleavage, enhancing antimicrobial activity. Beyond providing mechanistic insights into the role of proteasomes in cell-autonomous innate immunity, our study suggests that proteasome-cleaved peptides may have previously overlooked functions downstream of degradation. From a translational standpoint, identifying proteasome-derived defence peptides could provide an untapped source of natural antibiotics for biotechnological applications and therapeutic interventions in infectious diseases and immunocompromised conditions."
The team of researchers at Weizmann Institute
Fig. 1: Hundreds of potential antimicrobial peptides reside in the human proteome.
Staphylococcus bacteria that can cause human infections leading to immune failure.
Left: A culture of the untreated bacteria.
Right: A bacterial cell that has been destroyed by an antimicrobial peptide produced by the proteasome and discovered in the new study
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