Biology subjects

Adams, O.

Publications and source records attributed to Adams, O..

4 recordsLinked to original sources

bioRxiv2026

Cornichon receptors couple membrane adaptation to cargo selection during ER export.

Selective export of membrane proteins from the endoplasmic reticulum (ER) is fundamental for eukaryotic cell biology, yet how trafficking receptors coordinate cargo recognition with membrane adaptation and COPII recruitment remains unknown. Cornichon homolog (CNIH) proteins comprise a conserved family of trafficking receptors that mediate ER export of ion channels, G protein-coupled receptors (GPCRs), ATP-binding cassette (ABC) and solute carrier (SLC) transporters. Here, we determine cryo-electron microscopy structures of the prototypical cornichon receptor Erv14 bound to an SLC transporter in detergent and lipid nanodiscs. We show that cargo recognition is mediated by a dynamic network of interactions, in which structural lipids stabilize the receptor-cargo interface. Nanodisc structures reveal the assembly of a second Erv14 receptor that remodels the receptor-cargo interface in response to membrane architecture, thereby reducing local membrane thickness and providing direct structural evidence that cornichon receptors buffer hydrophobic mismatch during membrane protein biogenesis. Structural and trafficking analyses further show that the second receptor recruits the COPII adaptor Sec24, coupling membrane remodelling to cargo export. Together, our findings establish that cornichon receptors couple lipid-mediated membrane adaptation with cargo selection through sequential receptor assembly, linking membrane protein folding to selective COPII-mediated ER export. One sentence summaryCornichon receptors integrate membrane adaptation with cargo recognition to coordinate membrane protein quality control and selective ER export.

cell biology↗

bioRxiv2022

MMR vaccination induces a trained immunity program characterized by functional and metabolic reprogramming of γδ T cells

The measles, mumps and rubella (MMR) vaccine protects against all-cause mortality in children, but the immunological mechanisms mediating these effects are poorly known. We systematically investigated whether MMR can induce long-term functional changes in innate immune cells, a process termed trained immunity, that could at least partially mediate this heterologous protection. In a randomized placebo-controlled trial, 39 healthy adults received either the MMR vaccine or a placebo. By using single-cell RNA-sequencing, we found that MMR caused transcriptomic changes in CD14-positive monocytes and NK cells, but most profoundly in {gamma}{delta} T cells. Surprisingly, monocyte function was not altered by MMR vaccination. In contrast, the function of {gamma}{delta} T cells was significantly enhanced by MMR vaccination, with higher production of TNF and IFN{gamma}, as well as upregulation of cellular metabolic pathways. In conclusion, we describe a new trained immunity program characterized by modulation of {gamma}{delta} T cell function induced by MMR vaccination. One-sentence summaryMMR vaccination induces cellular and metabolic reprogramming in {gamma}{delta} T cells towards a more active phenotype.

immunology↗

bioRxiv2021

Design of D-amino acids SARS-CoV-2 Main protease inhibitors using the cationic peptide from rattlesnake venom as a scaffold

The C30 Endopeptidase (3C-like protease; 3CLpro) is essential for the life cycle of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) since it plays a pivotal role in viral replication and transcription and is hence a promising drug target. Molecules isolated from animals, insects, plants or microorganisms can serve as a scaffold for the design of novel biopharmaceutical products. Crotamine, a small cationic peptide from the venom of the rattlesnake Crotalus durissus terrificus has been the focus of many studies since it exhibits activities such as analgesic, in vitro antibacterial and hemolytic activities. The crotamine derivative L-peptides (L-CDP) that inhibit the 3CL protease in the low {micro}M range were examined since they are susceptible to proteolytic degradation; we explored the utility of their D-enantiomers form. Comparative uptake inhibition analysis showed D-CDP as a promising prototype for a D-peptide-based drug. We also found that the D-peptides can impair SARS-CoV-2 replication in vivo, probably targeting the viral protease 3CLpro.

biochemistry↗

bioRxiv2020

SARS-CoV-2 targets cortical neurons of 3D human brain organoids and shows neurodegeneration-like effects

COVID-19 pandemic caused by SARS-CoV-2 infection is a public health emergency. COVID-19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS-CoV-2 on the central nervous system (CNS). Here, we show that a Dusseldorf isolate of SARS-CoV-2 enters 3D human brain organoids within two days of exposure. Using COVID-19 convalescent serum, we identified that SARS-CoV-2 preferably targets soma of cortical neurons but not neural stem cells, the target cell type of ZIKA virus. Imaging cortical neurons of organoids reveal that SARS-CoV-2 exposure is associated with missorted Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Surprisingly, SARS-CoV-2 co-localizes specifically with Tau phosphorylated at Threonine-231 in the soma, indicative of early neurodegeneration-like effects. Our studies, therefore, provide initial insights into the impact of SARS-CoV-2 as a neurotropic virus and emphasize that brain organoids could model CNS pathologies of COVID-19. One sentence summaryCOVID-19 modeling in human brain organoids

cell biology↗