Biology subjects

Ibiricu, I.

Publications and source records attributed to Ibiricu, I..

3 recordsLinked to original sources

bioRxiv2026

Molecular mechanism of M1-mediated influenza A virus assembly

Influenza A virus assembly is orchestrated by matrix protein 1 (M1), which engages ribonucleoproteins, mediates glycoprotein incorporation, and scaffolds lipid envelopment, but how these activities are performed and coordinated is unclear. We determined high-resolution structures of M1 within virions, virus-like particles, and in vitro. We found that M1 binds phosphatidylinositol 4,5-bisphosphate at the membrane, oligomerizes through an electrostatic interface, and switches between three alternative conformational states in different regions of the virion. The M1 conformer at the front associates with ribonucleoproteins and initiates budding. In the body of the virion, two conformers alternate to create an extended filament with seam-like discontinuities. Enrichment of the seam-prone conformation at the virion rear induces envelope closure and exposes a binding site for the cytoplasmic tail of neuraminidase (NA) to promote virus release. Conformational switching within a polarized M1 lattice thereby couples organization of the viral components with shaping of the virion architecture.

microbiology↗

bioRxiv2023

PNMA2 forms non-enveloped virus-like capsids that trigger paraneoplastic neurological syndrome

The paraneoplastic Ma antigen (PNMA) genes are associated with cancer-induced paraneoplastic syndromes that present with neurological symptoms and autoantibody production. How PNMA proteins trigger a severe autoimmune disease is unclear. PNMA genes are predominately expressed in the central nervous system with little known functions but are ectopically expressed in some tumors. Here, we show that PNMA2 is derived from a Ty3 retrotransposon that encodes a protein which forms virus-like capsids released from cells as non-enveloped particles. Recombinant PNMA2 capsids injected into mice induce a robust autoimmune reaction with significant generation of autoantibodies that preferentially bind external "spike" PNMA2 capsid epitopes, while capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies present in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic neurologic disease show similar preferential binding to PNMA2 "spike" capsid epitopes. These observations suggest that PNMA2 capsids released from tumors trigger an autoimmune response that underlies Ma2 paraneoplastic neurological syndrome.

neuroscience↗

bioRxiv2021

In situ cryo-electron tomography reveals local cellular machineries for axon branch development

Neurons are highly polarized cells forming an intricate network of dendrites and axons. They are shaped by the dynamic reorganization of cytoskeleton components and cellular organelles. Axon branching allows to form new paths and increases circuit complexity. However, our understanding of branch formation is sparse due to technical limitations. Using in situ cellular cryo-electron tomography on primary mouse neurons, we directly visualized the remodeling of organelles and cytoskeleton structures at axon branches. Strikingly, branched areas functioned as hotspots concentrating organelles to support dynamic activities. Unaligned actin filaments assembled at the base of premature branches and remained while filopodia diminished. Microtubules and ER co-migrated into preformed branches to support outgrowth together with accumulating compact ~500 nm mitochondria and locally clustered ribosomes. We obtained a roadmap of events and present the first direct evidence of local protein synthesis selectively taking place at axon branches, allowing to serve as unique control hubs for axon development and downstream neural network formation.

neuroscience↗