Dual role of the RIG-I 2CARD as a signaling module and a brake on dsRNA translocation
- 1Kanazawa University
Abstract
RIG-I is an innate immune receptor for viral double-stranded RNA (dsRNA). Upon binding dsRNA, RIG-I nucleates MAVS filaments through its two caspase activation and recruitment domains (2CARD). However, how the 2CARD behaves during activation has remained unclear. Using high-speed atomic force microscopy, we visualized the 2CARD in full-length RIG-I across its apo, dsRNA-bound, translocating, multimeric, and polyubiquitin-bound states. Protrusions consistent with the 2CARD appeared only transiently in the apo state, whereas a mobile 2CARD emerged upon RNA binding. During ATP-driven translocation, wild-type RIG-I moved approximately twofold slower and showed more frequent pauses and multimers than RIG-I {Delta}2CARD. Within multimers, 2CARDs formed a complex that polyubiquitin stabilized into larger, dsRNA-deforming assemblies. These findings reveal the 2CARD as a brake on the RIG-I motor, beyond signaling.
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BibTeX
@misc{kondo2026dual,
title = {{Dual role of the RIG-I 2CARD as a signaling module and a brake on dsRNA translocation}},
author = {S. Kondo and J. Zhang and K. Matsushima and N. Kurihara and H. Flechsig and K. Umeda and N. Kodera and K. Kato and M. Shibata},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.13.758695},
url = {https://www.biorxiv.org/content/10.64898/2026.10.13.758695v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Dual role of the RIG-I 2CARD as a signaling module and a brake on dsRNA translocation
AU - S. Kondo
AU - J. Zhang
AU - K. Matsushima
AU - N. Kurihara
AU - H. Flechsig
AU - K. Umeda
AU - N. Kodera
AU - K. Kato
AU - M. Shibata
PY - 2026
DA - 2026/10/13
PB - bioRxiv
DO - 10.64898/2026.10.13.758695
UR - https://www.biorxiv.org/content/10.64898/2026.10.13.758695v1
AB - RIG-I is an innate immune receptor for viral double-stranded RNA (dsRNA). Upon binding dsRNA, RIG-I nucleates MAVS filaments through its two caspase activation and recruitment domains (2CARD). However, how the 2CARD behaves during activation has remained unclear. Using high-speed atomic force microscopy, we visualized the 2CARD in full-length RIG-I across its apo, dsRNA-bound, translocating, multimeric, and polyubiquitin-bound states. Protrusions consistent with the 2CARD appeared only transiently in the apo state, whereas a mobile 2CARD emerged upon RNA binding. During ATP-driven translocation, wild-type RIG-I moved approximately twofold slower and showed more frequent pauses and multimers than RIG-I {Delta}2CARD. Within multimers, 2CARDs formed a complex that polyubiquitin stabilized into larger, dsRNA-deforming assemblies. These findings reveal the 2CARD as a brake on the RIG-I motor, beyond signaling.
ER -