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TitleStructural basis for human RegⅢα filament formation.
Journal, issue, pagesCommun Chem, Vol. 9, Issue 1, Year 2026
Publish dateFeb 3, 2026
AuthorsJianting Han / Qin Cao /
PubMed AbstractRegIIIα is an antibacterial protein primarily operating in the digestive tract to defend against bacterial infection through direct bactericidal activity. A previous study proposed that RegIIIα ...RegIIIα is an antibacterial protein primarily operating in the digestive tract to defend against bacterial infection through direct bactericidal activity. A previous study proposed that RegIIIα forms hexameric pores on the membrane of Gram-positive bacteria, leading to cell lysis. These RegIIIα hexamers can further assemble into filaments, diminishing RegIIIα activity. However, the high-resolution structure of RegIIIα assembly remains elusive, impeding the comprehension of the molecular mechanisms underlying RegIIIα function. In this study, we determined the cryo-electron microscopy (cryo-EM) structure of RegIIIα filaments formed in vitro at a resolution of 2.2 Å. Our structure reveals a similar subunit arrangement but a distinct subunit orientation compared to the previously reported low-resolution model of RegIIIα filaments. Through structural analysis and biochemical assays, we identified two essential interfaces for RegIIIα assembly, offered a potential explanation for the necessity of lipids in RegIIIα assembly, and elucidated the inhibitory mechanism of the pro-segment of RegIIIα. Collectively, our study presents the first near-atomic structure of filaments formed by C-tyle lectin containing proteins, providing structural insights into RegIIIα assembly that are closely related to its physiological functions and regulations.
External linksCommun Chem / PubMed:41634150 / PubMed Central
MethodsEM (helical sym.)
Resolution2.21 Å
Structure data

EMDB-66219, PDB-9wtd:
Filament structure of human Reg3alpha
Method: EM (helical sym.) / Resolution: 2.21 Å

Source
  • homo sapiens (human)
KeywordsANTIMICROBIAL PROTEIN / C-type lectin domain containing protein / antimicrobial activity / cryo-EM / protein filament

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