Biology subjects

Zamora-Caballero, S.

Publications and source records attributed to Zamora-Caballero, S..

5 recordsLinked to original sources

bioRxiv2025

An unprecedented DNA recognition-mimicry switch governs induction in arbitrium phages

Temperate phages integrate multiple information sources to regulate lysis-lysogeny transitions. SPBeta-like phages use arbitrium signalling and DNA damage to control repressor activity during lytic induction, but how the repressor functions and is inactivated by the SOS response remains unclear. Here, we show that SroF, the SPBeta-like phage repressor, binds DNA via a novel mechanism involving its integrase-like fold, enabling stable prophage repression. Upon DNA damage, the host SOS response triggers derepression of a newly identified antirepressor, Sar. Sar binds SroF by mimicking the DNA structure recognised by the repressor, inactivating its function and inducing phage. This mechanism is conserved across SP{beta}-like phages, which encode multiple, specific SroF-Sar pairs. Surprisingly, repressor inactivation alone is insufficient for induction when arbitrium levels are high. Our results uncover the mechanism underlying the double layer of control that ensures phage induction occurs only under SOS conditions and in the absence of neighbouring prophages.

molecular biology↗

bioRxiv2025

Phages communicate across species to shape microbial ecosystems

Arbitrium is a communication system that helps bacteriophages decide between lysis and lysogeny via secreted peptides. In arbitrium, the AimP peptide binds its cognate AimR receptor to repress aimX expression, promoting lysogeny. It has been assumed that each AimR responds exclusively to its own AimP. Here, we question this view by demonstrating cross-communication between distinct arbitrium systems. Using prototypical arbitrium phages, we demonstrate that AimP peptides bind and repress unrelated AimR receptors, promoting lysogeny and reducing prophage induction. Structural and binding assays reveal conserved residues enabling cross-recognition while preserving specificity. In mixed lysogenic cultures, these interactions shape induction outcomes, demonstrating ecological relevance. We extent these findings to infection contexts, showing that arbitrium signalling influences outcomes in cells harbouring prophages with compatible communicating systems. These findings reveal that phages engage in cross-species communication, a trait restricted to more complex life forms, challenging our understanding of how these elements reshape microbial communities.

microbiology↗

bioRxiv2023

Architecture of the Vertebrate Egg Coat and Structural Basis of the ZP2 Block to Polyspermy

Post-fertilization cleavage of glycoprotein ZP2, a major subunit of egg zona pellucida (ZP) filaments, is crucial for mammalian reproduction by irreversibly blocking polyspermy. ZP2 processing is thought to inactivate a sperm-binding activity located upstream of the proteins cleavage site; however, its molecular consequences and connection with ZP hardening are unknown. Here we report X-ray crystallographic, cryo-EM and biochemical studies showing that cleavage of ZP2 triggers its oligomerization. Deletion of the ZP-N1 domain that precedes the cleavage site of mouse ZP2 allows it to homodimerize even without processing, and animals homozygous for this variant are subfertile by having a semi-hardened ZP that allows sperm attachment but hinders penetration. Combined with the structure of a native egg coat filament, which reveals the molecular basis of heteromeric ZP subunit interaction, this suggests that oligomerization of cleaved ZP2 cross-links the ZP, rigidifying it and making it physically impenetrable to sperm.

biophysics↗

bioRxiv2021

The structural role of SARS-CoV-2 genetic background in the emergence and success of spike mutations: the case of the spike A222V mutation

The S:A222V point mutation, within the G clade, was characteristic of the 20E (EU1) SARS-CoV-2 variant identified in Spain in early summer 2020. This mutation has now reappeared in the Delta subvariant AY.4.2, raising questions about its specific effect on viral infection. We report combined serological, functional, structural and computational studies characterizing the impact of this mutation. Our results reveal that S:A222V promotes an increased RBD opening and slightly increases ACE2 binding as compared to the parent S:D614G clade. Finally, S:A222V does not reduce sera neutralization capacity, suggesting it does not affect vaccine effectiveness.

molecular biology↗

bioRxiv2020

Cryo-EM Structure of Native Human Uromodulin, a Zona Pellucida Module Polymer

Assembly of extracellular filaments and matrices mediating fundamental biological processes such as morphogenesis, hearing, fertilization and antibacterial defense is driven by a ubiquitous polymerization module known as zona pellucida (ZP) "domain". Despite the conservation of this element from hydra to human, no information is available on the filamentous conformation of any ZP module protein. Here we report the cryo-electron microscopy structure of uromodulin (UMOD)/Tamm-Horsfall protein, the most abundant protein in human urine and an archetypal ZP module-containing molecule, in its mature homopolymeric state. UMOD forms a one-start helix with an unprecedented 180-degree twist between subunits enfolded by interdomain linkers that have completely reorganized as a result of propeptide dissociation. Lateral interaction between filaments in the urine generates sheets exposing a checkerboard of binding sites to capture uropathogenic bacteria, and UMOD-based models of mammalian and avian heteromeric egg coat filaments identify a common sperm-binding region at the interface between subunits.

biophysics↗