Dr. Roger Benoit
Scientist
Forschungsstrasse 111
5232 Villigen PSI
Switzerland
Research Interests
My research focuses on structure-based protein engineering. We explore the structural and biophysical basis of protein interactions, including receptor-drug, protein-protein, protein-toxin, protein-pathogen, protein-nucleic acid and protein-small molecule interactions. We apply structural elements found in natural proteins (molecular biomimetics) to engineer novel fusion proteins (protein nanotechnology) for a wide range of purposes. For example, my team and I have designed and produced fusion proteins containing intrinsically stable helical spacers to (1) introduce large cavities into crystal lattices (for the study of protein dynamics by crystallography); (2) develop self-assembling oligomeric protein scaffolds that display on their surface multiple copies of an epitope of choice at specific angles and distances (for the design of novel vaccines, structural vaccinology); and (3) produce rigid G-protein-coupled receptor (GPCR) fusion proteins that aid structure elucidation by cryo-EM of receptor-drug complexes. We furthermore explore novel fusion proteins as tools for in situ structural biology, both at near-atomic resolution and at the mesoscale (fluorescent sensors for the detection of important mesoscale cellular rearrangements involved in cancer metastasis; probes for the detection of toxin- or pathogen- receptors on cells; novel fusion proteins for the detection of proteins in large complexes in cryo-EM tomography).
Preprints
Farnung J., Muhar M., Liang J.R., Tolmachova K.A., Benoit R.M., Corn J.E., Bode J.W.
ATG3 contains a non-canonical LIR motif crucial for its enzymatic activity in autophagy
bioRxiv. 2022; doi: https://doi.org/10.1101/2022.08.02.502437
Collu G., Mohammed I., Lafita A., Bierig T., Poghosyan E., Bliven S., Benoit R.M.
Cryo-EM structure of a single-chain β1-adrenoceptor – AmpC β-lactamase fusion protein
bioRxiv. 2021; doi: https://doi.org/10.1101/2021.09.25.461805
Publications
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Collu G, Bierig T, Krebs A-S, Engilberge S, Varma N, Guixà-González R, et al.
Chimeric single α-helical domains as rigid fusion protein connections for protein nanotechnology and structural biology
Structure. 2022; 30(1): 95-106. https://doi.org/10.1016/j.str.2021.09.002
DORA PSI -
Bierig T, Collu G, Blanc A, Poghosyan E, Benoit RM
Design, expression, purification, and characterization of a YFP-tagged 2019-n CoV spike receptor-binding domain construct
Frontiers in Bioengineering and Biotechnology. 2020; 8: 618615 (10 pp.). https://doi.org/10.3389/fbioe.2020.618615
DORA PSI -
Skopintsev P, Ehrenberg D, Weinert T, James D, Kar RK, Johnson PJM, et al.
Femtosecond-to-millisecond structural changes in a light-driven sodium pump
Nature. 2020; 583: 314-318. https://doi.org/10.1038/s41586-020-2307-8
DORA PSI -
Krebs A-S, Bierig T, Collu G, Benoit RM
Seamless insert-plasmid assembly at sub-terminal homologous sequences
Plasmid. 2019; 106: 102445 (9 pp.). https://doi.org/10.1016/j.plasmid.2019.102445
DORA PSI -
Benoit RM
Botulinum neurotoxin diversity from a gene-centered view
Toxins. 2018; 10(8): 310 (14 pp.). https://doi.org/10.3390/toxins10080310
DORA PSI -
Benoit RM, Schärer MA, Wieser MM, Li X, Frey D, Kammerer RA
Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C
Scientific Reports. 2017; 7: 43588 (7 pp.). https://doi.org/10.1038/srep43588
DORA PSI -
Heydenreich FM, Miljuš T, Jaussi R, Benoit R, Milić D, Veprintsev DB
High-throughput mutagenesis using a two-fragment PCR approach
Scientific Reports. 2017; 7: 6787 (11 pp.). https://doi.org/10.1038/s41598-017-07010-4
DORA PSI -
Benoit RM, Ostermeier C, Geiser M, Li JSZ, Widmer H, Auer M
Seamless insert-plasmid assembly at high efficiency and low cost
PLoS One. 2016; 11(4): e0153158 (13 pp.). https://doi.org/10.1371/journal.pone.0153158
DORA PSI -
Bianchi S, van Riel WE, Kraatz SHW, Olieric N, Frey D, Katrukha EA, et al.
Structural basis for misregulation of kinesin KIF21A autoinhibition by CFEOM1 disease mutations
Scientific Reports. 2016; 6: 30668 (16 pp.). https://doi.org/10.1038/srep30668
DORA PSI -
Christen P, Jaussi R, Benoit R
Biochemie und Molekularbiologie. Eine Einführung in 40 Lerneinheiten
Berlin, Heidelberg: Springer; 2016. https://doi.org/10.1007/978-3-662-46430-4
DORA PSI -
Christen P, Jaussi R, Benoit R
Biomoleküle und ihre Wechselwirkungen
In: Christen P, Jaussi R, Benoit R, eds. Biochemie und Molekularbiologie. Eine Einführung in 40 Lerneinheiten. Berlin; Heidelberg: Springer; 2016:3-16. https://doi.org/10.1007/978-3-662-46430-4_1
DORA PSI -
Benoit RM, Frey D, Wieser MM, Thieltges KM, Jaussi R, Capitani G, et al.
Structure of the BoNT/A1 - Receptor complex
Toxicon. 2015; 107(Part A): 25-31. https://doi.org/10.1016/j.toxicon.2015.08.002
DORA PSI -
Benoit RM, Frey D, Hilbert M, Kevenaar JT, Wieser MM, Stirnimann CU, et al.
Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A
Nature. 2014; 505(7481): 108-111. https://doi.org/10.1038/nature12732
DORA PSI -
Kammerer RA, Benoit RM
Botulinum neurotoxins: new questions arising from structural biology
Trends in Biochemical Sciences. 2014; 39(11): 517-526. https://doi.org/10.1016/j.tibs.2014.08.009
DORA PSI -
Benoit RM, Meisner N-C, Kallen J, Graff P, Hemmig R, Cèbe R, et al.
The X-ray crystal structure of the first RNA recognition motif and site-directed mutagenesis suggest a possible hur redox sensing mechanism
Journal of Molecular Biology. 2010; 397(5): 1231-1244. https://doi.org/10.1016/j.jmb.2010.02.043
DORA PSI
Benoit R.M. and Auer M.
A direct way of redox sensing
RNA Biol. 2011; 8: 18-23
DOI: 10.4161/rna.8.1.13555
Meisner N.C., Hintersteiner M., Seifert J.M., Bauer R., Benoit R.M., Widmer A., Schindler T., Uhl V., Lang M., Gstach H., Auer M.
Terminal adenosyl transferase activity of posttranscriptional regulator HuR revealed by confocal on-bead screening.
J Mol Biol. 2009; 386: 435-450
DOI: 10.1016/j.jmb.2008.12.020
Benoit, R.M., Wilhelm, R.N., Scherer-Becker, D., Ostermeier, C.
An improved method for fast, robust, and seamless integration of DNA fragments into multiple plasmids.
Protein Expr Purif. 2006; 45: 66-71
DOI: 10.1016/j.pep.2005.09.022