9WTD

Filament structure of human Reg3alpha

Summary for 9WTD

• Entry DOI: 10.2210/pdb9wtd/pdb
• EMDB information: 5795 66219
• Descriptor: Regenerating islet-derived protein 3-alpha 15 kDa form (1 entity in total)
• Functional Keywords: c-type lectin domain containing protein, antimicrobial activity, cryo-em, protein filament, antimicrobial protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 12
• Total formula weight: 183468.59

Authors

Cao, Q.,Han, J.T. (deposition date: 2025-09-16, release date: 2026-02-11, Last modification date: 2026-03-25)

Primary citation

Han, J.,Cao, Q.
Structural basis for human RegIII alpha filament formation.
Commun Chem, 9:-, 2026

PubMed Abstract: 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.

PubMed: 41634150
DOI: 10.1038/s42004-026-01921-y

Experimental method

ELECTRON MICROSCOPY (2.21 Å)