PD Dr. Richard Alfred Kammerer

Photo of Richard Kammerer

Group Leader

Paul Scherrer Institute
Forschungsstrasse 111
5232 Villigen PSI
Switzerland

Botulinum neurotoxins (BoNTs) are among the most potent toxins known. They can cause botulism, a rare but potentially fatal paralytic disease and belong to the most dangerous bioweapons. Despite their toxicity, in particular BoNT/A1, commonly known as Botox, is used in cosmetic and medical applications. A detailed molecular understanding of BoNT/host protein interactions is fundamental both for developing strategies against botulism and for generating improved BoNT variants for medical applications.

 

Towards this aim, we are investigating toxin translocation and toxin/host receptor interactions. Furthermore, we are developing tools to study the structure and function of botulinum neurotoxins. To address these challenges, we use X-ray crystallography and cryo-electron microscopy (cryo-EM) in combination with biophysical, biochemical, and cell biological methods.

  1. Leka O, Wu Y, Li X, Kammerer RA. (2021) Crystal structure of the catalytic domain of botulinum neurotoxin subtype A3. J Biol Chem. 2021 Jan-Jun;296:100684. doi: 10.1016/j.jbc.2021.100684.
  2. Benoit RM, Schärer MA, Wieser MM, Li X, Frey D, Kammerer RA (2017) Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C.  Sci Rep. 2017 Mar 2; 7:43588. doi: 10.1038/srep43588.
  3. Kammerer RA, Benoit RM (2014) Botulinum neurotoxins: new questions arising from structural biology. Trends Biochem Sci. 2014 Nov;39(11):517-26. doi: 10.1016/j.tibs.2014.08.009.
  4. Benoit RM, Frey D, Hilbert M, Kevenaar JT, Wieser MM, Stirnimann CU, McMillan D, Ceska T, Lebon F, Jaussi R, Steinmetz MO, Schertler GF, Hoogenraad CC, Capitani G, Kammerer RA (2014) Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A. Nature. 2014 Jan 2;505(7481):108-11. doi: 10.1038/nature12732.

 

  • Nass KJ, Ilie IM, Saller MJ, Driessen AJM, Caflisch A, Kammerer RA, et al.
    The role of the N-terminal amphipathic helix in bacterial YidC: insights from functional studies, the crystal structure and molecular dynamics simulations
    Biochimica et Biophysica Acta: Biomembranes. 2022; 1864(3): 183825 (9 pp.). https://doi.org/10.1016/j.bbamem.2021.183825
    DORA PSI
  • Choo JPS, Kammerer RA, Li X, Li Z
    High-Level Production of Phenylacetaldehyde using Fusion-Tagged Styrene Oxide Isomerase
    Advanced Synthesis and Catalysis. 2021; 363(6): 1714-1721. https://doi.org/10.1002/adsc.202001500
    DORA PSI
  • Leka O, Wu Y, Li X, Kammerer RA
    Crystal structure of the catalytic domain of botulinum neurotoxin subtype A3
    Journal of Biological Chemistry. 2021; 296: 100684 (8 pp.). https://doi.org/10.1016/j.jbc.2021.100684
    DORA PSI
  • Fiedler T, Fabrice TN, Studer V, Vinet A, Faltova L, Kammerer RA, et al.
    Homodimerization of coronin A through the C-terminal coiled-coil domain is essential for multicellular differentiation of Dictyostelium discoideum
    FEBS Letters. 2020; 594(13): 2116-2127. https://doi.org/10.1002/1873-3468.13787
    DORA PSI
  • Li X, Brunner C, Wu Y, Leka O, Schneider G, Kammerer RA
    Structural insights into the interaction of botulinum neurotoxin a with its neuronal receptor SV2C
    Toxicon. 2020; 175: 36-43. https://doi.org/10.1016/j.toxicon.2019.11.010
    DORA PSI
  • Faltova L, Jiang K, Frey D, Wu Y, Capitani G, Prota AE, et al.
    Crystal structure of a heterotetrameric katanin p60:p80 complex
    Structure. 2019; 27(9): 1375-1383.e3. https://doi.org/10.1016/j.str.2019.07.002
    DORA PSI
  • Jiang K, Faltova L, Hua S, Capitani G, Prota AE, Landgraf C, et al.
    Structural basis of formation of the microtubule minus-end-regulating CAMSAP-katanin complex
    Structure. 2018; 26(3): 375-382. https://doi.org/10.1016/j.str.2017.12.017
    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
  • Jiang K, Rezabkova L, Hua S, Liu Q, Capitani G, Altelaar AFM, et al.
    Microtubule minus-end regulation at spindle poles by an ASPM-katanin complex
    Nature Cell Biology. 2017; 19(5): 480-492. https://doi.org/10.1038/ncb3511
    DORA PSI
  • Kaplan AR, Brady MR, Maciejewski MW, Kammerer RA, Alexandrescu AT
    Nuclear magnetic resonance structures of GCN4p are largely conserved when ion pairs are disrupted at acidic pH but show a relaxation of the coiled coil superhelix
    Biochemistry. 2017; 56(11): 1604-1619. https://doi.org/10.1021/acs.biochem.6b00634
    DORA PSI
  • Kumar A, Manatschal C, Rai A, Grigoriev I, Steiner Degen M, Jaussi R, et al.
    Short linear sequence motif LxxPTPh targets diverse proteins to growing microtubule ends
    Structure. 2017; 25(6): 924-932. https://doi.org/10.1016/j.str.2017.04.010
    DORA PSI
  • Rezabkova L, Jiang K, Capitani G, Prota AE, Akhmanova A, Steinmetz MO, et al.
    Structural basis of katanin p60:p80 complex formation
    Scientific Reports. 2017; 7: 14893 (8 pp.). https://doi.org/10.1038/s41598-017-14194-2
    DORA PSI
  • Vercellino I, Rezabkova L, Olieric V, Polyhach Y, Weinert T, Kammerer RA, et al.
    Role of the nucleotidyl cyclase helical domain in catalytically active dimer formation
    Proceedings of the National Academy of Sciences of the United States of America PNAS. 2017; 114(46): E9821-E9828. https://doi.org/10.1073/pnas.1712621114
    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
  • Hilbert M, Noga A, Frey D, Hamel V, Guichard P, Kraatz SHW, et al.
    SAS-6 engineering reveals interdependence between cartwheel and microtubules in determining centriole architecture
    Nature Cell Biology. 2016; 18(4): 393-403. https://doi.org/10.1038/ncb3329
    DORA PSI
  • Rezabkova L, Kraatz SHW, Akhmanova A, Steinmetz MO, Kammerer RA
    Biophysical and structural characterization of the centriolar protein CEP104 interaction network
    Journal of Biological Chemistry. 2016; 291(35): 18496-18504. https://doi.org/10.1074/jbc.M116.739771
    DORA PSI
  • Sharma A, Aher A, Dynes NJ, Frey D, Katrukha EA, Jaussi R, et al.
    Centriolar CPAP/SAS-4 imparts slow processive microtubule growth
    Developmental Cell. 2016; 37(4): 362-376. https://doi.org/10.1016/j.devcel.2016.04.024
    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
  • Alfieri A, Ong ACM, Kammerer RA, Solanky T, Bate S, Tasab M, et al.
    Angiopoietin-1 regulates microvascular reactivity and protects the microcirculation during acute endothelial dysfunction: role of eNOS and VE-cadherin
    Pharmacological Research. 2014; 80: 43-51. https://doi.org/10.1016/j.phrs.2013.12.008
    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
  • Jayachandran R, Liu X, BoseDasgupta S, Müller P, Zhang C-L, Moshous D, et al.
    Coronin 1 regulates cognition and behavior through modulation of cAMP/Protein kinase A signaling
    PLoS Biology. 2014; 12(3): e1001820 (21 pp.). https://doi.org/10.1371/journal.pbio.1001820
    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
  • Stroud MJ, Nazgiewicz A, McKenzie EA, Wang Y, Kammerer RA, Ballestrem C
    GAS2-like proteins mediate communication between microtubules and actin through interactions with end-binding proteins
    Journal of Cell Science. 2014; 127(12): 2672-2682. https://doi.org/10.1242/jcs.140558
    DORA PSI
  • Weber S, Stirnimann CU, Wieser M, Frey D, Meier R, Engelhardt S, et al.
    A type IV translocated Legionella cysteine phytase counteracts intracellular growth restriction by phytate
    Journal of Biological Chemistry. 2014; 289(49): 34175-34188. https://doi.org/10.1074/jbc.M114.592568
    DORA PSI
  • Bjelić S, Wieser M, Frey D, Stirnimann CU, Chance MR, Jaussi R, et al.
    Structural basis for the oligomerization-state switch from a dimer to a trimer of an engineered cortexillin-1 coiled-coil variant
    PLoS One. 2013; 8(5): e63370 (7 pp.). https://doi.org/10.1371/journal.pone.0063370
    DORA PSI
  • Prota AE, Magiera MM, Kuijpers M, Bargsten K, Frey D, Wieser M, et al.
    Structural basis of tubulin tyrosination by tubulin tyrosine ligase
    Journal of Cell Biology. 2013; 200(3): 259-270. https://doi.org/10.1083/jcb.201211017
    DORA PSI
  • Bjelić S, De Groot CO, Schärer MA, Jaussi R, Bargsten K, Salzmann M, et al.
    Interaction of mammalian end binding proteins with CAP-Gly domains of CLIP-170 and p150glued
    Journal of Structural Biology. 2012; 177(1): 160-167. https://doi.org/10.1016/j.jsb.2011.11.010
    DORA PSI
  • Beecher N, Roseman AM, Jowitt TA, Berry R, Troilo H, Kammerer RA, et al.
    Collagen VI, conformation of A-domain arrays and microfibril architecture
    Journal of Biological Chemistry. 2011; 286(46): 40266-40275. https://doi.org/10.1074/jbc.M111.265595
    DORA PSI
  • Stroud MJ, Kammerer RA, Ballestrem C
    Characterization of G2L3 (GAS2-like 3), a new microtubule- and actin-binding protein related to spectraplakins
    Journal of Biological Chemistry. 2011; 286(28): 24987-24995. https://doi.org/10.1074/jbc.M111.242263
    DORA PSI
  • Ciani B, Bjelić S, Honnappa S, Jawhari H, Jaussi R, Payapilly A, et al.
    Molecular basis of coiled-coil oligomerization-state specificity
    Proceedings of the National Academy of Sciences of the United States of America PNAS. 2010; 107(46): 19850-19855. https://doi.org/10.1073/pnas.1008502107
    DORA PSI

Jaussi,Rolf Dr.
Project Leader

Meury,Marcel Dr.
Postdoc

Rezabkova,Lenka Dr.
Postdoc
E-mail: lenka.rezabkova@chem.ethz.ch

Thieltges,Katherine Marie
Technician

Zimmermann,Mirjam Dr.
Research assistant