Department of Biochemistry University of Oxford Department of Biochemistry
University of Oxford
South Parks Road
Oxford OX1 3QU

Tel: +44 (0)1865 613200
Fax: +44 (0)1865 613201
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John Vakonakis
Structural Biology and Biophysics

Co-workers: Dr. George Hatzopoulos, Dr. Dirk Reiter, Ms. Leanne Slater, Mr. Kacper Rogala, Ms. Erin Cutts, Ms. Julia Binder, Ms. Alison Inglis, Mr. Martin Masik, Mr. Niklas Laasch

Group website

Structural biology has been immensely successful in elucidating the high-resolution structures of macromolecular compounds. The challenge we face now is assembling these components into larger units. The group focuses on two large assemblies of medical relevance; the first is linked to pathogenic cytoadherence during severe malaria, while the second, centrioles, are cell organelles crucial for cell division, motility and sensing.

Malaria is a parasitic disease virtually absent in the developed world, but that still affects developing countries strongly. Most malaria deaths are caused by a single parasite species, Plasmodium falciparum, and many can be attributed to obstruction of small blood vessels in tissues by red blood cell clumps. Cytoadherence of infected erythrocytes is mediated by a system unique to P. falciparum that includes the PfEMP1 protein family and other parasite components.

Our research focus is on understanding how this parasite system alters erythrocyte properties including their shape, flexibility and adhesion to epithelial cells. Large protrusions, called “knobs”, develop on the erythrocyte surface and are essential for disease pathology. Yet, we do not know how “knobs” assemble or their internal structure. Important questions to be addressed include how PfEMP1 anchors to the erythrocyte cytoskeleton, how it localizes in “knobs” and how KHARP, another parasite component, alters the mechanical properties of the erythrocyte cytoskeleton.

Centrioles, the major component of animal centrosomes, must duplicate once per cell cycle in order to maintain their number. Abnormalities in this duplication cycle can lead to medical conditions such ciliopathies, male sterility and cancer. It is therefore important to understand how these structures assemble, and how their assembly is regulated by the cell. Genetic analysis uncovered a number of proteins, including SAS-6, SAS-4/CPAP and SAS-5/STIL, as being important for this process. Structural biologists need to place these components now in the context of the centriolar assembly.

Recently, we and co-workers showed that SAS-6 is the first structural component in this assembly process. SAS-6 forms a large, multimeric framework that determines centriolar symmetry and allows other components to attach. Now, we need to address how this process is regulated, and how the pro-centriolar framework matures.

To address these questions, the laboratory uses NMR spectroscopy, X-ray crystallography and other biophysical techniques. To bridge the gaps between high-resolution structures, large assemblies and whole cells we also collaborate with groups doing electron microscopy, tomography and in vivo molecular biology.

Recent news items

Different routes to building symmetry in cell structures

BBSRC funding success for Dr. Vakonakis' work on centriole assembly

Single protein holds hey to building up cell structures


Selected recent publications

1. Hatzopoulos, G.N., Erat, M.C., Cutts, E., Rogala, K.B., Slater, L.M., Stansfeld, P.J., Vakonakis, I. (2013) Structural analysis of the G-Box domain of the microcephaly protein CPAP suggests a role in centriole architecture. Structure 21, 2069-77.
2. Hilbert, M., Erat, M.C., Hachet, V., Guichard, P., Blank, I.D., Flückiger, I., Slater, L., Lowe, E.D., Hatzopoulos, G.N., Steinmetz, M.O., Gönczy, P. and Vakonakis, I. (2013) The Caenorhabditis elegans centriolar protein SAS-6 can form a spiral that is consistent with imparting a 9-fold symmetry. Proc. Natl. Acad. Sci. U.S.A. 110, 11373-8.
3. Erat, M.C., Sladek, B., Campbell, I.D. and Vakonakis, I. (2013) Structural analysis of collagen type I interactions with human fibronectin reveals a cooperative binding mode. J Biol Chem. 288, 17441-50.
4. Mayer, C., Slater, L., Erat, M.C., Konrat, R., Vakonakis, I. (2012) Structural analysis of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) intracellular domain reveals a conserved interaction epitope. J Biol Chem. 287, 7182-9.
5. Kitagawa, D., Vakonakis, I., Olieric, N., Hilbert, M., Keller, D., Olieric, V., Bortfeld, M., Erat, M.C., Flückiger, I., Gönczy, P., Steinmetz, M.O. (2011) Structural Basis of the 9-Fold Symmetry of Centrioles. Cell 144, 364-75.
6. Erat, M.C., Schwarz-Linek, U., Pickford, A.R., Farndale, R.W., Campbell, I.D., Vakonakis, I. (2010) Implications for collagen binding from the crystallographic structure of fibronectin 6FnI1-2FnII7FnI. J Biol Chem. 285, 33764-70.
7. Vakonakis, I., Staunton, D., Ellis, I.R., Sarkies, P., Flanagan, A., Schor, A.M., Schor, S.L. and Campbell, I.D. (2009) Motogenic sites in human fibronectin are masked by long range interactions. J Biol Chem. 284, 15668-75.
8. Erat, M.C., Slatter, D.A., Lowe, E.D., Millard, C.J., Farndale, R.W., Campbell, I.D. and Vakonakis, I. (2009) Identification and structural analysis of type I collagen sites in complex with fibronectin fragments. Proc. Natl. Acad. Sci. U.S.A. 106, 4195-200.


More Publications...

Research Images

Cartoon showing how the nine-fold symmetric cartwheel model determines the overall symmetry of centrioles, drawn as ensembles of microtubule blades. An electron micrograph of C. reinhardtii SAS-6 protein with clearly visible ring structures is shown in the background.
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