Year: 2026
Type: article
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. RegIIIα is an antibacterial protein that forms hexametric pores on Gram-positive bacterial membranes leading to cell lysis, however, hexamers can further assemble into filaments diminishing RegIIIα activity. Here, the authors use cryo-electron microscopy to reveal the 2.2 Å structure of RegIIIα filaments, uncovering a distinct subunit orientation and key interfaces for RegIIIα assembly, proposing the inhibitory mechanism of the pro-segment of RegIIIα.
Source: Communications Chemistry
Authors: Jianting Han, Qin Cao
Institution: Shanghai Jiao Tong University
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,690
Award: G5216395784
OpenAlex ID: W7127284055