We thrive to understand the molecular mechanism underlying the interaction of the intestinal microbiome with the human host. We focus on bacteria that are overrepresented in the microbiome of colorectal cancer (CRC) patients and the interactions of bacterial adhesins with epithelial and immune cells of the intestinal system. Genomic sequencing, big data analysis, and substantial microbial studies in animal models identified important drivers of CRC on the microbial and cellular level, but the underlying mechanistic details are not known. Therefore, we structurally analyze complexes between commensal proteins and human receptors to understand the molecular background of their binding mechanisms.
We apply cryogenic electron microscopy (Cryo-EM) and single particle analysis to determine the structures of protein complexes that facilitate the host-microbiome interaction, which is a prerequisite for structure-based design of personalized anticancer compounds. In addition, we visualize molecular details of bacteria interacting with the host epithel via cryo-ET to understand their binding mechanisms in a cellular context. Finally, we attempt to identify yet undescribed bacterial adhesins that facilitate epithelial binding in a pathogenic context using genomic and biochemical screening systems.
Research SectionStructural Biology
Open positions for MSc students (minimum 6 months) in the field of cryo-EM and single particle analysis of an adhesin-receptor complex. For further information, please contact D. Roderer via email.
Mechanism of threonine ADP-ribosylation of F-actin by a Tc toxin
Site-specific N-glycan profiles of α<sub>5</sub> β<sub>1</sub> integrin from rat liver.
Biology of the cell 2022read online
Structure of a Tc holotoxin pore provides insights into the translocation mechanism
Lethal injections with unique injection mechanism,Giftspritzen mit einzigartigem Injektionsmechanismus
BioSpektrum 2019read online
Common architecture of Tc toxins from human and insect pathogenic bacteria
Science Advances 2019read online
Tc toxin complexes: Assembly, membrane permeation, and protein translocation
Annual Review of Microbiology 2019read online
SPHIRE-crYOLO is a fast and accurate fully automated particle picker for cryo-EM
Communications Biology 2019read online
Towards the application of Tc toxins as a universal protein translocation system
Nature Communications 2019read online
Membrane insertion of a Tc toxin in near-atomic detail
Nature Structural and Molecular Biology 2016read online
Soluble oligomers of the pore-forming toxin cytolysin a from Escherichia coli are off-pathway products of pore assembly
Journal of Biological Chemistry 2016read online
Acceleration of the Rate-Limiting Step of Thioredoxin Folding by Replacement of its Conserved cis-Proline with (4S)-Fluoroproline
ChemBioChem 2015read online
The assembly dynamics of the cytolytic pore toxin ClyA
Nature Communications 2015read online
Acceleration of protein folding by four orders of magnitude through a single amino acid substitution
Scientific Reports 2015read online
M. Shafaq-Zadah*, E. Dransart, C. Wunder, V. Chambon, C. A. Valades-Cruz, L. Leconte, N. Kumar Sarangi, J. Robinson, S. Bai, R. Regmi, A. Di Cicco, A. Hovasse, R. Bartels, U. Nilsson, S. Cianférani-Sanglier, H. Leffler, T. Keyes, D. Lévy, S. Raunser, D. Roderer*, L. Johannes*. Spatial N-glycan rearrangement on α5β1 integrin nucleates galectin-3 oligomers to determine endocytic fate. Preprint at bioRxiv, 2023. doi: 10.1101/2023.10.27.564026.