This work characterize Chp1, a membrane-embedded CARF effector that assembles as a tetrameric pore harboring autoinhibitory lipid fenestrations that occlude the pore in the inactive state, and uncover a lipid-gated mechanism that expands the repertoire of CRISPR-mediated defense strategies.
Abstract
Prokaryotic Type III CRISPR–Cas systems synthesize cyclic oligoadenylate (cOA) second messengers that activate CRISPR-associated Rossmann fold (CARF) immune effectors during viral infection. Here we characterize Chp1, a membrane-embedded CARF effector that assembles as a tetrameric pore harboring autoinhibitory lipid fenestrations that occlude the pore in the inactive state. cOA binding triggers a structural rearrangement that (i) closes the fenestrations, (ii) eliminates the lipid obstruction of the pore to open it, and (iii) remodels the pore entrance from hydrophobic to polar to allow ion permeation. This conformational switch triggers depolarization of the membrane of the infected cell, which enters growth arrest and becomes inhospitable for viral replication. Our results uncover a lipid-gated mechanism that expands the repertoire of CRISPR-mediated defense strategies.
Findings provide direct experimental evidence that the α-1 helix participates in ABC transporter-mediated membrane insertion and pore formation through its translocation, thereby advancing the understanding of the molecular mechanism underlying Cry toxin pore assembly.
Zi-Bo Cui, Wei Ding, Meng-Chen Pu et al.· International Journal of Bio...· 0 citations
This work introduces BEAM, a multiscale framework that learns slow collective variables from coarse-grained simulations to guide all-atom enhanced sampling to explain how vectorial secretion accelerates pertactin folding by excluding an off-pathway kinetic trap.
Lan Yang, Qing Luan, Michael C. Baxa et al.· bioRxiv· 0 citations
Peptidoglycan biogenesis requires membrane flippases to translocate lipid-linked precursors across the cytoplasmic membrane for processing. This essential step is mediated by MurJ, the lipid II flippase conserved across all peptidoglycan-producing bacteria. While MurJ from diderm bacteria has been structurally resolved...
Yan-Cheng E. Li, Grace F. Baron, W. Clemons· Journal of Biological Chemis...· 0 citations
Outdoor membrane stiffness is revealed as a previously unrecognized physical basis of multidrug tolerance and modulating bacterial envelope mechanics may provide new opportunities for antimicrobial intervention, suggesting that modulating bacterial envelope mechanics may provide new opportunities for antimicrobial inte...
Nan Xiao, Bo Zheng, Jia-Feng Liu· bioRxiv· 0 citations
The nuclear pore complex (NPC) was initially viewed as a passive gateway for molecular transport, but it is now recognized as an active and highly selective signaling hub that orchestrates nucleocytoplasmic communication. In plants, dissection of the NPC's intricate architecture has revealed its critical role in innate...
Wei Dou, Feng-Hui Xu, Xin-Yi Cai et al.· Plant Science· 0 citations
Biological processes are often regulated through reactions involving supramolecular protein complexes organized with nanoscale precision, such as the apoptosome that activates procaspase-9 through defined stoichiometry to induce apoptosis. Here we report designer CASCAD (CARD Assembly on SCAffold DNA), a self-assembled...
Dhanush Gandavadi, A. Dwivedy, Revathi Manoharaan et al.· bioRxiv· 0 citations
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