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Laboratory for Nanoscale Biology

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Dr. Roger Benoit

Roger Benoit

Scientist

Paul Scherrer Institute
Forschungsstrasse 111
5232 Villigen PSI
Switzerland
Telephone
+41 56 310 47 03
Email
roger.benoit@psi.ch

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Curriculum Vitae

Team

Research Interests

My research focuses on the molecular basis of subtle structural changes that enable biased signaling by G protein-coupled receptors (GPCRs). Recent biophysical evidence suggests that GPCRs, a key family of drug targets, are not merely on/off switches of signal transmission. Rather, the transmission of extracellular signals to the cell interior by GPCRs involves a wide range of dynamic intermediate structural conformations in response to different ligands or drugs (biased signaling). Crystallization of GPCRs is nowadays feasible, but typically requires the investigation of hundreds of constructs and the production milligram amounts of conformationally homogeneous proteins that are stable over a period of several weeks. Stabilized GPCRs embedded in a crystal lattice may not retain all the important subtle conformational changes induced by specific ligands or drugs. Emerging technologies in electron cryo-microscopy (cryo-EM) now provide new possibilities that will in the near future enable structure elucidation of GPCRs from single particles. The key challenge is to engineer GPCR-containing particles that fit the requirements for cryo-EM data collection and analysis. Our understanding of structural rearrangements is complemented by 3D-electron diffraction from crystals or particles, as well as time-resolved X-ray crystallography (Swiss-FEL) experiments. These novel methodologies are expected to unveil new structural details, allowing a deeper understanding of the signaling mechanisms and providing a solid platform for structure-based drug design.

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Publications

  • 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

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Laboratory of Nanoscale Biology

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Anita Strittmatter
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Paul Scherrer Institut
Department of Biology and Chemistry
OFLC/108
Forschungsstrasse 111
CH-5232 Villigen PSI
Switzerland

Phone: +41 56 310 20 35
Fax: +41 56 310 21 99
anita.strittmatter@psi.ch

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