Speaker
Description
Massive, catalytically active protein cages are exceptionally rare in nature. The oral pathogen Porphyromonas gingivalis secretes zuzalysin (ZUZ), a virulence metallopeptidase that undergoes a calcium-triggered hierarchical assembly. Activated via a cysteine-switch mechanism, ZUZ pentamers sequentially organize into bipentamers, tripentamers, and a colossal, virus-like ≈5.6-MDa dodecahedral particle DdhZUZ. Seven X-ray and cryo-EM structures (1.8–3.6 Å) reveal the molecular basis of this activation and self-assembly. The physiological DdhZUZ cage features 60 internal active sites accessible only to small substrates through twenty ≈45-Å pores. Measuring ≈355 Å in diameter, DdhZUZ is the largest naturally occurring, catalytically active homomeric protein assembly resolved to high resolution, surpassing major peptidase complexes and metabolic cores in both size and structural clarity.