PD Dr. Richard Alfred Kammerer

Curriculum Vitae

Botulinum neurotoxin A (BoNT/A), commonly known as Botox, is the most toxic substance known and causes human botulism, a rare but potentially fatal paralytic disease. Despite its toxicity, BoNT/A is used as an effective therapeutic for the treatment of a wide range of neuronal and neuromuscular disorders. BoNT/A is probably best known for its application as an anti-wrinkle agent. 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 have recently determined a crystal structure of BoNT/A in complex with its protein receptor synaptic vesicle glycoprotein 2C (SV2C). The complex crystal structure has important implications for BoNT/A function.

G-protein coupled receptors (GPCRs) are integral membrane proteins that share a common seven-transmembrane helix fold topology. They play fundamental roles in most physiological and many pathological processes. Currently, GPCRs are the target of ~30% of all medical drugs. As a result of the major drug discovery activities targeting GPCRs, there is a growing demand for high-resolution structures. Despite enormous efforts, however, progress in the structural characterization of GPCRs is rather slow. Primarily two methods have been developed for structural work on GPCRs: scanning alanine mutagenesis and the fusion protein engineering approach. However, both methods have substantial limitations, emphasizing that the development of new GPCR crystallization tools will be of fundamental importance in moving the field forward. Towards this aim, we developed a novel approach to facilitate the crystallization of GPCRs.

The overarching aims of our research are to understand BoNT/A-host protein interactions at the molecular detail and to develop new GPCR crystallization tools. For our studies, we use biochemical, biophysical and structural biological techniques.

• Structural Basis of Formation of the Microtubule Minus-End-Regulating CAMSAP-Katanin Complex Jiang K, Faltova L, Hua S, Capitani G, Prota Andrea E, Landgraf C, Volkmer R, Kammerer Richard A, Steinmetz Michel O, Akhmanova A
  STRUCTURE -, S0969212617304422 (2018).
  DOI: 10.1016/j.str.2017.12.017

• Baculovirus-based genome editing in primary cells Mansouri M, Ehsaei Z, Taylor V, Berger P
  PLASMID 90, 5 (2017).
  DOI: 10.1016/j.plasmid.2017.01.003
• Comprehensive Analysis of the Role of Arrestin Residues in Receptor Binding Haider Raphael S, Rizk A, Schertler G, Ostermaier M
  Springer International Publishing -, 83 (2017).
  DOI: 10.1007/978-3-319-57553-7_7
• Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C Benoit RM, Schaerer MA, Wieser MM, Li X, Frey D, Kammerer RA
  Scientific Reports 7, 43588 (2017).
  DOI: 10.1038/srep43588
• Microtubule minus-end regulation at spindle poles by an ASPM-katanin complex. Jiang K, Rezabkova L, Hua S, Liu Q, Capitani G, Maarten Altelaar AF, Heck AJR, Kammerer RA, Steinmetz MO, Akhmanova A
  NATURE CELL BIOLOGY 19, 480 (2017).
  DOI: 10.1038/NCB3511
• Role of the nucleotidyl cyclase helical domain in catalytically active dimer formation. Vercellino I, Rezabkova L, Olieric V, Polyhach Y, Weinert T, Kammerer RA, Jeschke G, Korkhov VM
  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 114, E9821 (2017).
  DOI: 10.1073/PNAS.1712621114
• Short Linear Sequence Motif LxxPTPh Targets Diverse Proteins to Growing Microtubule Ends. Kumar A, Manatschal C, Rai A, Grigoriev I, Degen MS, Jaussi R, Kretzschmar I, Prota AE, Volkmer R, Kammerer RA, Akhmanova A, Steinmetz MO
  STRUCTURE 25, 924 (2017).
  DOI: 10.1016/J.STR.2017.04.010
• Structural basis of katanin p60:p80 complex formation Rezabkova L, Jiang K, Capitani G, Prota Andrea E, Akhmanova A, Steinmetz Michel O, Kammerer Richard A
  Scientific Reports 7, 14893 (2017).
  DOI: 10.1038/s41598-017-14194-2

• Accelerating the Association of the Most Stable Protein-Ligand Complex by more than Two Orders of Magnitude Giese C, Eras J, Kern A, Schärer Martin A, Capitani G, Glockshuber R
  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION , (2016).
  DOI: 10.1002/anie.201603652
• Biophysical and Structural Characterization of the Centriolar Protein Cep104 Interaction Network. Rezabkova L, Kraatz SH, Akhmanova A, Steinmetz MO, Kammerer RA
  JOURNAL OF BIOLOGICAL CHEMISTRY 291, 18496 (2016).
  DOI: 10.1074/JBC.M116.739771
• Centriolar CPAP/SAS-4 Imparts Slow Processive Microtubule Growth Sharma Ashwani, Aher Amol, Dynes Nicola J, Frey Daniel, Katrukha Eugene A, Jaussi Rolf, Grigoriev Ilya, Croisier Marie, Kammerer Richard A, Akhmanova Anna, Gonczy Pierre, Steinmetz Michel O
  DEVELOPMENTAL CELL 37, 362-376 (2016).
  DOI: 10.1016/j.devcel.2016.04.024
• SAS-6 engineering reveals interdependence between cartwheel and microtubules in determining centriole architecture Hilbert Manuel, Noga Akira, Frey Daniel, Hamel Virginie, Guichard Paul, Kraatz Sebastian H W, Pfreundschuh Moritz, Hosner Sarah, Flueckiger Isabelle, Jaussi Rolf, Wieser Mara M, Thieltges Katherine M, Deupi Xavier, Mueller Daniel J, Kammerer Richard A, Goenczy Pierre, Hirono Masafumi, Steinmetz Michel O
  NATURE CELL BIOLOGY 18, 393-+ (2016).
  DOI: 10.1038/ncb3329
• Structural basis for misregulation of kinesin KIF21A autoinhibition by CFEOM1 disease mutations Bianchi S, van Riel Wilhelmina E, Kraatz Sebastian HW, Olieric N, Frey D, Katrukha Eugene A, Jaussi R, Missimer J, Grigoriev I, Olieric V, Benoit Roger M, Steinmetz Michel O, Akhmanova A, Kammerer Richard A
  Scientific Reports 6, 30668 (2016).
  DOI: 10.1038/srep30668

• Functional roles of the hexamer organization of plant glutamate decarboxylase Astegno A, Capitani G, Dominici P
  BIOCHIMICA ET BIOPHYSICA ACTA (BBA) - PROTEINS AND PROTEOMICS 1854, 1229 (2015).
  DOI: 10.1016/j.bbapap.2015.01.001
• Structure of the BoNT/A1 - receptor complex Benoit Roger M, Frey D, Wieser Mara M, Thieltges Katherine M, Jaussi R, Capitani G, Kammerer Richard A
  TOXICON 107, 25 (2015).
  DOI: 10.1016/j.toxicon.2015.08.002
• Time-resolved structural studies with serial crystallography: A new light on retinal proteins Panneels Valerie, Wu Wenting, Tsai ChingJu, Nogly Przemek, Rheinberger Jan, Jaeger Kathrin, Cicchetti Gregor, Gati Cornelius, Kick Leonhard M, Sala Leonardo, Capitani Guido, Milne Chris, Padeste Celestino, Pedrini Bill, Li XiaoDan, Standfuss Joerg, Abela Rafael, Schertler Gebhard
  STRUCTURAL DYNAMICS 2, 041718 (2015).
  DOI: 10.1063/1.4922774

• 7 angstrom resolution in protein two-dimensional-crystal X-ray diffraction at Linac Coherent Light Source Pedrini Bill, Tsai Ching-Ju, Capitani Guido, Padeste Celestino, Hunter Mark S, Zatsepin Nadia A, Barty Anton, Benner W Henry, Boutet Sebastien, Feld Geoffrey K, Hau-Riege Stefan P, Kirian Richard A, Kupitz Christopher, Messerschmitt Marc, Ogren John I, Pardini Tommaso, Segelke Brent, Williams Garth J, Spence John C H, Abela Rafael, Coleman Matthew, Evans James E, Schertler Gebhard F X, Frank Matthias, Li Xiao-Dan
  PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES 369, UNSP 20130500 (2014).
  DOI: 10.1098/rstb.2013.0500
• A Type IV Translocated Legionella Cysteine Phytase Counteracts Intracellular Growth Restriction by Phytate Weber Stephen, Stirnimann Christian U, Wieser Mara, Frey Daniel, Meier Roger, Engelhardt Sabrina, Li Xiaodan, Capitani Guido, Kammerer Richard A, Hilbi Hubert
  JOURNAL OF BIOLOGICAL CHEMISTRY 289, 34175-34188 (2014).
  DOI: 10.1074/jbc.M114.592568
• Conformational transitions driven by pyridoxal-5 '-phosphate uptake in the psychrophilic Serine hydroxymethyltransferase from Psychromonas ingrahamii Angelaccio Sebastiana, Dworkowski Florian, Di Bello Angela, Milano Teresa, Capitani Guido, Pascarella Stefano
  PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS 82, 2831-2841 (2014).
  DOI: 10.1002/prot.24646
• Coronin 1 Regulates Cognition and Behavior through Modulation of cAMP/Protein Kinase A Signaling Dalva M, Jayachandran R, Liu X, BoseDasgupta S, Müller P, Zhang C, Moshous D, Studer V, Schneider J, Genoud C, Fossoud C, Gambino F, Khelfaoui M, Müller C, Bartholdi D, Rossez H, Stiess M, Houbaert X, Jaussi R, Frey D, Kammerer Richard A, Deupi X, de Villartay J, Lüthi A, Humeau Y, Pieters J
  PLOS BIOLOGY 12, e1001820 (2014).
  DOI: 10.1371/journal.pbio.1001820
• How Periplasmic Thioredoxin TlpA Reduces Bacterial Copper Chaperone ScoI and Cytochrome Oxidase Subunit II (CoxB) Prior to Metallation Abicht Helge K, Schaerer Martin A, Quade Nick, Ledermann Raphael, Mohorko Elisabeth, Capitani Guido, Hennecke Hauke, Glockshuber Rudi
  JOURNAL OF BIOLOGICAL CHEMISTRY 289, (2014).
  DOI: 10.1074/jbc.M114.607127
• Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A Benoit Roger M, Frey Daniel, Hilbert Manuel, Kevenaar Josta T, Wieser Mara M, Stirnimann Christian U, McMillan David, Ceska Tom, Lebon Florence, Jaussi Rolf, Steinmetz Michel O, Schertler Gebhard F X, Hoogenraad Casper C, Capitani Guido, Kammerer Richard A
  NATURE 505, 108-+ (2014).
  DOI: 10.1038/nature12732
• Structural basis for-10 promoter element melting by environmentally induced sigma factors Campagne Sebastien, Marsh May E, Capitani Guido, Vorholt Julia A, Allain Frederic H-T
  NATURE STRUCTURAL & MOLECULAR BIOLOGY 21, 269-276 (2014).
  DOI: 10.1038/nsmb.2777
• Structure, Activity, and Stability of Atomically Dispersed Rh in Methane Steam Reforming Duarte RB, Krumeich F, van Bokhoven JA
  ACS CATALYSIS 4, 1279 (2014).
  DOI: 10.1021/cs400979q
• Transient Mechanistic Studies of Methane Steam Reforming over Ceria-Promoted Rh/Al2O3 Catalysts Duarte RB, Olea M, Iro E, Sasaki T, Itako K, van Bokhoven JA
  CHEMCATCHEM 6, 2898 (2014).
  DOI: 10.1002/cctc.201402388

• (4R)- and (4S)-Fluoroproline in the Conserved cis-Prolyl Peptide Bond of the Thioredoxin Fold: Tertiary Structure Context Dictates Ring Puckering Rubini Marina, Schaerer Martin A, Capitani Guido, Glockshuber Rudi
  CHEMBIOCHEM 14, 1053-1057 (2013).
  DOI: 10.1002/cbic.201300178
• Quaternary Dynamics of the SecA Motor Drive Translocase Catalysis Gouridis G, Karamanou S, Sardis MF, Schaerer MA, Capitani G, Economou A
  MOLECULAR CELL 52, 655-666 (2013).
  DOI: 10.1016/j.molcel.2013.10.036
• Structural Basis for the Oligomerization-State Switch from a Dimer to a Trimer of an Engineered Cortexillin-1 Coiled-Coil Variant Bjelic Sasa, Wieser Mara, Frey Daniel, Stirnimann Christian U, Chance Mark R, Jaussi Rolf, Steinmetz Michel O, Kammerer Richard A
  PLOS ONE 8, e63370 (2013).
  DOI: 10.1371/journal.pone.0063370

• A Prokaryotic S1P Lyase Degrades Extracellular S1P In Vitro and In Vivo: Implication for Treating Hyperproliferative Disorders Ho P, Huwiler A, Bourquin F, Kotelevets N, Pastukhov O, Capitani G, Grütter Markus G, Zangemeister-Wittke U
  PLOS ONE 6, e22436 (2011).
  DOI: 10.1371/journal.pone.0022436
• Integration of multiple expression cassettes into mammalian genomes in a single step Kriz A, Schmid K, Ballmer K, Berger P
  Protocol Exchange , (2011).
  DOI: 10.1038/protex.2011.249
• RNA polymerase I?specific subunits promote polymerase clustering to enhance the rRNA gene transcription cycle Albert B, Léger-Silvestre I, Normand C, Ostermaier M, Pérez-Fernández J, Panov Kostya I, Zomerdijk Joost CBM, Schultz P, Gadal O
  The Journal of Cell Biology 192, 277 (2011).
  DOI: 10.1083/jcb.201006040

• Automated seamless DNA co-transformation cloning with direct expression vectors applying positive or negative insert selection Olieric N, Kuchen M, Wagen S, Sauter M, Crone S, Edmondson S, Frey D, Ostermeier C, Steinmetz M, Jaussi R
  BMC BIOTECHNOLOGY 10, 56 (2010).
  DOI: 10.1186/1472-6750-10-56

• Automated unrestricted multigene recombineering for multiprotein complex production Bieniossek C, Nie Y, Frey D, Olieric N, Schaffitzel C, Collinson I, Romier C, Berger P, Richmond T, Steinmetz M, Berger I
  NATURE METHODS 6, 447 (2009).
  DOI: 10.1038/nmeth.1326
• Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models Leal A, Huehne K, Bauer F, Sticht H, Berger P, Suter U, Morera B, Del Valle G, Lupski James R, Ekici A, Pasutto F, Endele S, Barrantes R, Berghoff C, Berghoff M, Neundörfer B, Heuss D, Dorn T, Young P, Santolin L, Uhlmann T, Meisterernst M, Sereda M, zu Horste G, Nave K, Reis A, Rautenstrauss B
  NEUROGENETICS 10, 275 (2009).
  DOI: 10.1007/s10048-009-0183-3
• Mutation of His465 Alters the pH-dependent Spectroscopic Properties of Escherichia coli Glutamate Decarboxylase and Broadens the Range of Its Activity toward More Alkaline pH Pennacchietti E, Lammens TM, Capitani G, Franssen MCR, John RA, Bossa F, De Biase D
  JOURNAL OF BIOLOGICAL CHEMISTRY 284, 31587 (2009).
  DOI: 10.1074/jbc.M109.049577

• Anti-Mullerian-hormone-dependent regulation of the brain serine-protease inhibitor neuroserpin Lebeurrier N, Launay S, Macrez R, Maubert E, Legros H, Leclerc A, Jamin SP, Picard JY, Marret S, Laudenbach V, Berger P, Sonderegger P, Ali C, di Clemente N, Vivien D
  JOURNAL OF CELL SCIENCE 121, 3357 (2008).
  DOI: 10.1242/jcs.031872
• Crystal structure of the ternary FimC-FimF(t)-FimD(N) complex indicates conserved pilus chaperone-subunit complex recognition by the usher FimD Eidam O, Dworkowski FSN, Glockshuber R, Grutter MG, Capitani G
  FEBS LETTERS 582, 651 (2008).
  DOI: 10.1016/j.febslet.2008.01.030
• Molecular evolution of B6 enzymes: Binding of pyridoxal-5'-phosphate and Lys41Arg substitution turn ribonuclease A into a model B6 protoenzyme Vacca R, Giannattasio S, Capitani G, Marra E, Christen P
  BMC BIOCHEMISTRY 9, 17 (2008).
  DOI: 10.1186/1471-2091-9-17

• Mtmr13/Sbf2-deficient mice: an animal model for CMT4B2 Tersar K, Boentert M, Berger P, Bonneick S, Wessig C, Toyka KV, Young P, Suter U
  HUMAN MOLECULAR GENETICS 16, 2991 (2007).
  DOI: 10.1093/hmg/ddm257
• Multiprotein Expression Strategy for Structural Biology of Eukaryotic Complexes Fitzgerald Daniel J, Schaffitzel C, Berger P, Wellinger R, Bieniossek C, Richmond Timothy J, Berger I
  STRUCTURE 15, 275 (2007).
  DOI: 10.1016/j.str.2007.01.016
• Production of in vitro amplified DNA pseudolibraries and high-throughput cDNA target amplification Frey D, Kambach C, Steinmetz M, Jaussi R
  BMC BIOTECHNOLOGY 7, 31 (2007).
  DOI: 10.1186/1472-6750-7-31

• Multi-level regulation of myotubularin-related protein-2 phosphatase activity by myotubularin-related protein-13/set-binding factor-2 Berger P, Berger I, Schaffitzel C, Tersar K, Volkmer B, Suter U
  HUMAN MOLECULAR GENETICS 15, 569 (2006).
  DOI: 10.1093/hmg/ddi473
• Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease Niemann A, Berger P, Suter U
  NEUROMOLECULAR MEDICINE 8, 217 (2006).
  DOI: 10.1385/NMM:8:1:217
• Protein complex expression by using multigene baculoviral vectors Fitzgerald D, Berger P, Schaffitzel C, Yamada K, Richmond T, Berger I
  NATURE METHODS 3, 1021 (2006).
  DOI: 10.1038/nmeth983
• Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot-Marie-Tooth disease) Berger P, Niemann A, Suter U
  GLIA 54, 243 (2006).
  DOI: 10.1002/glia.20386

• COMP-Ang1: A designed angiopoietin-1 variant with nonleaky angiogenic activity Cho CH, Kammerer RA, Lee HJ, Steinmetz MO, Ryu YS, Lee SH, Yasunaga K, Kim KT, Kim I, Choi HH, Kim W, Kim SH, Park SK, Lee GM, Koh GY
  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 101, 5547-5552 (2004).
  DOI: 10.1073/pnas.0307574101

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