Structural biology of the cytoskeleton

Project leader: Inari Kursula, Ph.D., Asst.Prof.

Department of Biochemistry, University of Oulu, P.O. Box 3000, 90014 University of Oulu, Finland
and
CSSB-HZI and University of Hamburg at DESY, Notkestrasse 85, Bldg. 25b, 22607 Hamburg, Germany
e-mail: inari.kursula(at)oulu.fi, inari.kursula(at)helmholtz-hzi.de
More information on our group:
http://www.desy.de/~inari/lab
http://www.desy.de/~inari/hzi.html

Research interests

Cytoskeletal proteins recognize and bind to each other. Actin - the central protein of the cytoskeleton - polymerizes to form complex structures together with other components of the cytoskeleton and various regulatory proteins. Pathogens use these cytoskeletal complexes for both motility and invasion of their host cells. Once these mechanisms are understood at the molecular - or atomic - level, we can look for ways to interfere with the processes of motility and invasion.

We study the motility and host cell invasion of the parasite causing malaria, which is one of the world's most devastating infectious diseases. Each year, more than a million people die of malaria. The disease is caused by Plasmodium spp., which comprise a group of unicellular, eukaryotic, intracellular parasites. They use actin for motility and invasion of host cells but their cytoskeleton differs markedly from that of higher eukaryotes. Actin filaments of Plasmodium and related parasites are extremely short, and their rapid treadmilling is regulated by a strikingly small number of actin-binding proteins.

It is these proteins that are in the limelight of our research group: How do the three-dimensional structures of these proteins look like? What do the complexes they form look like and how do they work? How can we interfere with their function? Answers to these questions can be found by means of X-ray crystallography and small-angle X-ray scattering, combined with other biophysical and biochemical methodology. We aim to shed light on the structure and function of these proteins and complexes, using new methods based on the accelerator technologies at DESY: making large structures of the cytoskeleton visible - at high resolution - using most modern synchrotron radiation sources.

Recent publications

• 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., Article ID 671439, 14 pages. doi:10.4061/2011/671439.
• Patel AK, Yadav RP, Majava V, Kursula I & Kursula P (2011) Structure of the dimeric autoinhibited conformation of DAPK2, a pro-apoptotic protein kinase. J. Mol. Biol., 409: 369-383.
• 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 J & 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.
• 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 Y-H, 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.
  

Group members

In Oulu:

• Alexander Ignatev, Ph.D.
• Juha Vahokoski, M.Sc.
• S.P. Bhargav, M.Sc.
• Esa-Pekka Kumpula, M.Sc.
• Markku Soronen, student

In Hamburg (CSSB-HZI at DESY):

• Thorsten Mengesdorf, Ph.D.
• Juha Kallio, Ph.D.
• Moon Chatterjee, M.Sc.
• Gopinath Muruganandam, M.Sc.
• Nele Vervaet, M.Sc.
• Susanne Meier, technician