New bioRxiv preprint on native entanglement misfolding and yeast proteome aging

Native entanglement misfolding and age-associated structural change across the yeast proteome. — Native entanglement misfolding can create long-lived, near-native states that help explain age-associated structural changes in the yeast proteome.

Our new bioRxiv preprint, “Native entanglement misfolding contributes to age-associated structural changes across the Saccharomyces cerevisiae proteome,” is now available.

In this work, we ask whether native non-covalent lasso entanglements create intrinsic structural vulnerabilities that become visible during proteome aging. By combining limited proteolysis mass spectrometry data from aging yeast, structural annotations, and molecular simulations, we find that globular proteins predicted to undergo entanglement-mediated misfolding are enriched among proteins with age-associated structural changes.

The results support a topology-centered view of proteome aging: some proteins may become vulnerable not only because cellular quality control declines with age, but because their native folds contain entanglements that can populate persistent, near-native misfolded states.