Inari Kursula

Position

Professor

Affiliation

Research groups

Research

I am a structural biologist, interested in cell motility and in particular how malaria parasites move and invade their host cells. I did my PhD in structural biology at the University of Oulu, Finland, in 2003. After post-doctoral stays at the EMBL Hamburg Outstation and the Karolinska Institute, I have led my own research group in Oulu since 2008. In parallel, I have been a junior group leader at the Helmholtz Centre for Infection Research at CSSB/DESY in Hamburg (2009-2015), Academy of Finland Research Fellow (2012-2017), a 20% professor at the University of Bergen (2014-2017), and a visiting scientist at the European XFEL (2015-). Since 2017, my main position is at the Department of Biomedicine, University of Bergen.

Research in my group is focused on understanding malaria parasite gliding motility at the molecular/atomic level. For this aim, we use a broad range of structural biology and biochemical/biophysical methods.

No. of publications: 56 - No. of citations: 1815 - h-index: 26

Teaching

Methods in Biomedical Research - BMED320

Publications

2023

  • Hung YF, Chen Q, Pires I, Han H, Rosenthal PB & Kursula I (2023) Structure of Toxoplasma gondii glideosome-associated connector suggests a role as an elastic element in actomyosin force generation for gliding motility. Preprint available on bioRxiv: https://doi.org/10.1101/2022.12.09.519741.

  • Dans MG, Piirainen H, Nguyen W, Khurana S, Mehra S, Razook Z, Geoghegan ND, Dawson AT, Das S, Schneider MP, Jonsdottir TK, Gabriela M, Gancheva MR, Tonkin C, Mollard V, Goodman CD, McFadden GI, Wilson DW, Rogers KL, Barry AE, Crabb BS, de-Koning-Ward TF, Sleebs BE, Kursula I & Gilson PR (2023) The sulfonylpiperazine MMV020291 prevents red blood cell invasion by the malaria parasite Plasmodium falciparum through interference with actin-1/profilin dynamics. PLoS Biol 21: e3002066.

  • Lopez AJ, Andreadaki M, Vahokoski J, Deligianni E, Calder LJ, Camerini S, Freitag A, Bergmann U, Rosenthal PB, Sidén-Kiamos I & Kursula I (2023) Structure and function of Plasmodium actin II in the parasite mosquito stages. PLoS Pathog 19: e1011174. 

2022

  • Pires I, Hung YF, Bergmann U, Molloy JE & Kursula I (2022) Analysis of Plasmodium falciparum myosin B ATPase activity and structure in complex with the calmodulin-like domain of its light chain MLC-B. J Biol Chem in press, https://doi.org/10.1016/j.jbc.2022.102634

  • Vahokoski J, Calder L, Lopez AJ, Molloy JE, Kursula I & Rosenthal PB (2022) High-resolution structures of malaria parasite actomyosin and actin filaments. PLoS Pathog 18: e1010408.

  • Bendes ÁÁ, Kursula P & Kursula I (2022) Structure and function of an atypical homodimeric actin capping protein from the malaria parasite. Cell Mol Life Sci 79: 125.

2021

  • Han H, Round E, Schubert R, Gül Y, Makroczyová J, Meza D, Heuser P, Aepfelbacher M, Barák I, Betzel C, Fromme P, Kursula I, Nissen P, Tereschenko E, Schulz J, Uetrecht C, Ulicný J, Wilmanns M, Hajdu J, Lamzin VS & Lorenzen K. (2021) The XBI BioLab for life science experiments at the European XFEL. J Appl Crystallogr 54: 7-21.

  • Bustad HJ, Kallio JP, Laitaoja M, Toska K, Kursula I, Martinez A & Jänis J (2021) Characterization of porphobilinogen deaminase mutants reveals that arginine-173 is crucial for polypyrrole elongation mechanism. iScience 24: 102152.

2020

  • Makumire S, Zininga T, Vahokoski J, Kursula I & Shonhai A (2020) Biophysical analysis of Plasmodium falciparum Hsp70-Hsp90 organising protein (PfHop) reveals a monomer that is characterised by folded segments connected by flexible linkers. PLoS ONE 15: 0226657.

  • Bendes ÁÁ, Chatterjee M, Götte B, Kursula P & Kursula I (2020) Functional homo- and heterodimeric actin capping proteins from the malaria parasite. Biochem Biophys Res Commun 525: 681-686.

  • Moreau CA, Quadt KA, Piirainen H, Kumar H, Bhargav SP, Strauss L, Tolja NH, Wade RC, Spatz JP, Kursula I & Frischknecht F (2020) Optical tweezers uncover a function of profilin in force generation during malaria parasite motility independent of actin binding. J Cell Sci 134: jcs233775.

2019

  • Kumpula EP, Lopez AJ, Tajedin L, Han H & Kursula I (2019) Atomic view into Plasmodium actin polymerization, ATP hydrolysis, and fragmentation. PLoS Biol 17: e3000315.

  • Saghaug CS, Klotz C, Kallio JP, Brattbakk HR, Stokowy T, Aebischer T, Kursula I, Langeland N & Hanevik K (2019) Genetic variation in metronidazole metabolism and oxidative stress pathways in clinical Giardia lamblia assemblage A and B isolates. Infect Drug Resist 12: 1221-1235.

  • Szigetvari PD, Muruganandam G, Kallio JP, Hallin EI, Fossbakk A, Loris R, Kursula I, Møller LB, Knappskog PM, Kursula P & Haavik J (2019) The quaternary structure of human tyrosine hydroxylase: effects of dystonia-associated missense variants on oligomeric state and enzyme activity. J Neurochem 148: 291-306.

2018

  • Mukherjee B, Tessaro F, Vahokoski J, Kursula I, Marq JB, Scapozza L & Soldati-Favre D (2018) Modeling and resistant alleles explain the selectivity of antimalarial compound 49c towards apicomplexan aspartyl proteases. EMBO J 37: e98047.

2017

  • Pino P, Caldelari R, Mukherjee B, Vahokoski J, Klages N, Maco B, Collins CR, Blackman MJ, Kursula I, Heussler V, Brochet M & Soldati-Favre D (2017) A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress. Science 358: 522-528.

  • Kumpula EP, Pires IP, Lasiwa D, Piirainen H, Bergmann U, Vahokoski J & Kursula I (2017) Apicomplexan actin polymerization depends on nucleation. Sci Rep 7: 12137.

  • Pospich S, Kumpula EP, von der Ecken J, Vahokoski J, Kursula I & Raunser S (2017) Near-atomic structure of jasplakinolide-stabilized malaria parasite F-actin reveals the structural basis of filament instability. Proc Natl Acad Sci 114: 10636-10641.

  • Green JL, Wall RJ, Vahokoski J, Yusuf NA, Ridzuan MAM, Stanway RR, Stock J, Knuepfer E, Brady D, Martin SR, Howell SA, Pires IP, Moon RW, Molloy JE, Kursula I, Tewari R & Holder AA (2017) Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility. J Biol Chem 292: 17857-17875.

  • Panneerselvam S, Kumpula EP, Kursula I, Burkhardt A & Meents A (2017) Rapid cadmium SAD phasing at the standard wavelength (1 Å). Acta Cryst D 73: 581-590.

  • Moreau C, Bhargav SP, Kumar H, Quadt KA, Piirainen H, Strauss L, Kehrer J, Streichfuss M, Spatz J, Wade R, Kursula I & Frischknecht F (2017) A unique profilin-actin interface is important for malaria parasite motility. PLoS Pathog 13: e1006412.

  • Muruganandam G, Raasakka A, Myllykoski M, Kursula I & Kursula P (2017) Structural similarities and functional differences point to evolutionary relationship between tRNA healing enzymes and the myelin enzyme CNPase. BMC Biochem 18: 7.

2016

  • Jacot D, Tosetti N, Pires I, Stock J, Graindorge A, Hung YF, Han H, Tewari R, Kursula I & Soldati-Favre D (2016) An apicomplexan actin-binding protein serves as a connector and lipid sensor to coordinate motility and invasion. Cell Host Microbe 20: 731-743.

  • Mueller C, Samoo A, Hammoudi PM, Klages N, Kallio JP, Kursula I & Soldati-Favre D (2016) Structural and functional dissection of Toxoplasma gondii armadillo repeats only protein. J Cell Sci 129: 1031-1045.

2015

  • Raasakka A, Myllykoski M, Laulumaa S, Lehtimäki M, Haertlein M, Moulin M, Kursula I & Kursula P (2015) Determinants of ligand binding and catalytic activity in the myelin enzyme 2',3-cyclic nucleotide 3'-phosphodiesterase. Sci Rep 5: 16520.
  • Bhargav SP, Vahokoski J, Kallio JP, Torda AE, Kursula P & Kursula I (2015) Two independently folding units of Plasmodium profilin suggest evolution via gene fusion. Cell Mol Life Sci 72: 4193-4203.
  • Kumpula EP & Kursula I (2015) Towards a molecular understanding of the apicomplexan actin motor – on a road to novel targets for malaria remedies? Acta Cryst F 71: 500-513.

2014

  • Salamun J, Kallio JP, Daher W, Soldati-Favre D & Kursula I (2014) Structure of Toxoplasma gondii coronin – an actin-binding protein that relocalizes to the posterior pole of invasive parasites and contributes to invasion and egress. FASEB J 28: 4729-4747.
  • Vahokoski J, Bhargav SP, Desfosses A, Andreadaki M, Kumpula EP, Muñico Martinez S, Ignatev A, Lepper S, Frischknecht F, Sidén-Kiamos I, Sachse C & Kursula I (2014) Structural differences explain diverse functions of Plasmodium actins. PLoS Pathog 10: e1004091.
  • Kallio JP & Kursula I (2014) Recombinant production, purification, and crystallization of the Toxoplasma gondii coronin WD40 domain. Acta Cryst F 70: 517-521.
  • Ruskamo S, Yadav RP, Sharma S, Lehtimäki M, Laulumaa S, Aggarwal S, Simons M, Bürck J, Ulrich AS, Juffer AH, Kursula I & Kursula P (2014) Atomic-resolution view into structure-function relationships of human myelin peripheral membrane protein P2. Acta Cryst D 70: 165-176.

2013

  • Muruganandam G, Bürck J, Ulrich AS, Kursula I & Kursula P (2013) Lipid membrane association of myelin proteins and peptide segments studied by oriented and synchrotron radiation circular dichroism spectroscopy. J Phys Chem B 117: 14983-14993.
  • Vervaet N, Kallio JP, Meier S, Salmivaara E, Eberhardt M, Zhang S, Sun X, Wu Z, Kursula P & Kursula I (2013) Recombinant production, crystallization, and preliminary structural characterization of Schistosoma japonicum profilin. Acta Cryst F 69: 1264-1267.
  • Bhargav SP, Vahokoski J, Kumpula EP & Kursula I (2013) Crystallization and preliminary structural characterization of the two actin isoforms of the malaria parasite. Acta Cryst F 69: 1171-1176.

  • Wedderhoff I, Kursula I, Groves MR & Ortiz de Orué Lucana D (2013) Iron binding at specific sites within the octameric HbpS protects streptomycetes from iron-mediated oxidative stress. PLoS ONE 8: e71579.
  • Myllykoski M, Raasakka A, Lehtimäki M, Han H, Kursula I & Kursula P (2013) Crystallographic analysis of the reaction cycle of 2',3'-cyclic nucleotide 3'-phosphodiesterase, a member of the 2H phosphoesterase family. J Mol Biol 425: 4307-4322.

2012

  • Ruskamo S, Chukhlieb M, Vahokoski J, Bhargav SP, Liang F, Kursula I & Kursula P (2012) Juxtanodin is an intrinsically disordered F-actin binding protein. Sci Rep 2: 899.
  • Myllykoski M, Itoh K, Kangas SM, Heape AM, Kang SU, Lubec G, Kursula I & Kursula P (2012) Direct molecular interaction of the myelin enzyme 2’,3’-cyclic nucleotide 3’-phosphodiesterase with the calcium sensor calmodulin. J Neurochem 123: 515-524.
  • Ignatev A, Bhargav SP, Vahokoski J, Kursula P & Kursula I (2012) The lasso segment is required for functional dimerization of the Plasmodium formin 1 FH2 domain. PLoS ONE 7: e33586.

2011

  • Singh BK, Sattler JM, Chatterjee M, Huttu J, Schüler H & Kursula I (2011) Crystal structures explain functional differences in the two actin depolymerization factors of the malaria parasite. J Biol Chem 286: 28256-28264.
  • Nilsson S, Moll K, Angeletti D, Albrecht L, Kursula I, Jiang N, Sun X, Berzins K, Wahlgren M & Chen Q (2011) Characterization of the Duffy-binding like domain of Plasmodium falciparum blood-stage antigen 332. Malaria Res Treat 2011: 671439.
  • Patel AK, Yadav RP, Majava V, Kursula I & Kursula P (2011) Structure of the pro-apoptotic protein kinase DAPK2, a member of the death-associated protein kinase family J Mol Biol 409: 369-383.

2010

  • Huttu J, Singh BK, Bhargav SP, Sattler JM, Schüler H & Kursula I (2010) Crystallization and preliminary structural characterization of the two actin depolymerization factors of the malaria parasite. Acta Cryst F 66: 583-587.
  • Majava V, Polverini E, Mazzini A, Nanekar R, Knoll W, Peters J, Natali F, Baumgärtel P, Kursula I & Kursula P (2010) Structural and functional characterization of human peripheral nervous system myelin protein P2. PLoS ONE 5: e10300.
  • Wigren E, Bourhis JM, Kursula I, Guy JE & Lindqvist Y (2010) Crystal structure of the LMAN1-CRD/MCFD2 transport receptor complex provides insight into combined deficiency of Factor V and Factor VIII. FEBS Lett 584: 878-882.

2008

  • Kursula I, Kursula P, Ganter M, Panjikar S, Matuschewski K & Schüler H (2008) Structural basis for parasite‐specific functions of the divergent profilin of Plasmodium falciparum. Structure 16: 1638-1648.
  • Kursula P, Kursula I, Massimi M, Song YH, Downer, J, Stanley WA, Witke W & Wilmanns M (2008) High‐resolution structural analysis of mammalian profilin 2a complex formation with two physiological ligands: formin homology 1 domain of mDia1 and the proline rich domain of VASP. J Mol Biol 375: 270‐290.

2007

  • Sultana A, Alexeev I, Kursula I, Mäntsälä P, Niemi J & Schneider G (2007) Structure determination by multiwavelength anomalous diffraction of aclacinomycin oxidase: indications of multidomain pseudomerohedral twinning. Acta Cryst D 63: 149‐159.

2006

  • Müller S, Kursula I, Zou P & Wilmanns M (2006) Crystal structure of the PB1 domain of NBR1. FEBS Lett 581: 341‐344.

2005

  • Kursula I, Heape AM & Kursula P (2005) Crystal structure of non‐fused glutathione‐S-transferase from Schistosoma japonicum in complex with glutathione. Protein Pept Lett 12: 709‐712.

2004

  • Kursula I, Salin M, Sun J, Norledge BV, Haapalainen AM, Sampson NS & Wierenga RK (2004) Understanding protein lids: Structural analysis of active hinge mutants in triosephosphate isomerase. Protein Eng Des Sel 17: 375‐382.

2003

  • Kursula I & Wierenga RK (2003) Crystal structure of triosephosphate isomerase complexed with 2‐phosphoglycolate at 0.83‐Å resolution. J Biol Chem 278: 9544‐9551.

2002

  • Kursula I, Partanen S, Lambeir AM & Wierenga RK (2002) The importance of the conserved Arg191‐Asp227 salt bridge of triosephosphate isomerase for folding, stability, and catalysis. FEBS Lett 518: 39‐42.

2001

  • Kursula I, Partanen S, Lambeir AM, Antonov DM, Augustyns K & Wierenga RK (2001) Structural determinants for ligand binding and catalysis of triosephosphate isomerase. Eur J Biochem 268: 5189‐5196.

2000

  • Lambeir AM, Backmann J, Ruiz‐Sanz J, Filimonov V, Nielsen JE, Kursula I, Norledge BV & Wierenga RK (2000) The ionisation of Glu65 buried at the monomer‐monomer interface in Leishmana mexicana triosephosphate isomerase is thermodynamically linked to the stability of the dimer. Eur J Biochem 267: 2516‐2524.

1999

  • Pospiech H, Kursula I, Abdel‐Aziz W, Malkas L, Uitto L, Kastelli M, Vihinen‐Ranta M, Eskelinen S & Syväoja JE (1999) A neutralizing antibody against human DNA polymerase ε inhibits cellular but not SV40 DNA replication. Nucleic Acids Res 27: 3799‐3804.

 

2023
2022
2021
2020
2019
2018
2017
2016
2015

See a complete overview of publications in Cristin.

Projects

Molecular mechanisms of parasite motility

Work in my research group is aimed at a mechanistic understanding of gliding motility, which malaria parasites and their relatives use for getting to and invading their host cells. We employ a broad range of biochemical, biophysical and hybrid structural biology methods for creating a complete molecular picture of the parasite actin-myosin motor and the entire glideosome. We also want to understand the evolution of apicomplexan gliding motility and eukaryotic actin-myosin motors in a broader sense. Understanding the mechanistic differences in cell motility between parasites and humans may, furthermore, open up new avenues for treatment and/or prevention of malaria.

We have determined atomic structures of malaria parasite actins in both monomeric and filamentous form and characterized their polymerization properties as well as nearly all the parasite actin-binding proteins known to date. Our future work is directed more towards larger complexes and reconstructing the entire parasite glideosome for structural and functional characterization.

My research group is divided between the Faculty of Biochemistry and Molecular Medicine at the University of Oulu, Finland, and the Department of Biomedicine, University of Bergen, Norway.