This scientist found a new trick of the immune system by digging through cellular rubbish
Summary
Yifat Merbl and her team at the Weizmann Institute discovered that the cell’s proteasome — a barrel-shaped protein ‘shredder’ — produces antimicrobial peptide fragments from ordinary cellular proteins. Using mass spectrometry and database comparisons, the group identified about 1,000 proteasome-derived peptides with sequences similar to known bactericidal peptides, and computationally estimated more than 270,000 possible antimicrobial fragments across the human proteome.
Crucially, when cells are infected by bacteria the proteasome swaps its regulatory cap for one that biases production towards these bacteria-fighting peptides. This mechanism appears to act as a rapid, cell-intrinsic first line of defence that operates independently of classical immune-cell activation. The findings were published in Nature (Goldberg et al., 2025) and have generated notable excitement in the field.
Key Points
- The proteasome, beyond protein degradation, generates peptide fragments with antimicrobial activity.
- Mass spectrometry identified ~1,000 natural proteasome-derived peptides that match known bactericidal sequences.
- Computational analysis suggests >270,000 potential antimicrobial peptides could be produced from normal human proteins.
- Proteasomes change regulatory caps during bacterial infection to favour production of antimicrobial peptides — a cell-autonomous defence.
- The peptides arise from common cellular proteins, meaning single genes can encode multiple, previously hidden functions.
Context and relevance
This discovery reframes the proteasome from a mere ‘recycling’ machine to an active contributor to innate defence. It links basic cell biology with immunology and suggests cells can quickly deploy antimicrobial peptides without waiting for immune-cell recruitment. The finding has implications for understanding host–pathogen interactions, innate immunity, and could inform new antimicrobial strategies at a time when antibiotic resistance is a growing concern.
Why should I read this?
Because it’s a neat bit of detective work that flips a familiar cellular process into a surprising weapon. If you care about how the body fights infection, or about clever ways evolution squeezes more function from the same genes, this is exactly the kind of twisty, important story worth five minutes of your time.
Author style
Punchy: This is a significant, paradigm-shifting observation — simple in concept but broad in consequence. Read the paper if you want the experimental details; the summary gets you the headline, but the methods show how convincing the evidence is.