Home | Research | NMR facilities | Group Specific | Contact Info

John Vakonakis's Research

During the last couple of decades structural biology has been tremendously successful, as evidenced by the thousands of high-resolution structures available at RCSB. Our task now shifts to Structural Cell Biology: placing these structures into physiologically relevant, large-scale assemblies. This is a demanding task, since traditional tools like X-ray crystallography and NMR do not scale well by size. However, integrating these tools with new techniques, such as super-resolution optical microscopy, electron microscopy and tomography, and modeling may help to bridge the size gap.

Our group tries to tackle two such medically important assemblies. The first are large (~ 20nm x 100nm) protrusions, called 'knobs', that form on the surface of malaria-infected erythrocytes. 'Knob' formation is essential for development of severe malaria cases, responsible for the vast majority of deaths from the disease. We are trying to determine how parasite and human erythrocyte proteins interact and come together to form these assemblies. Our second system involves formation of centrioles, the primary component of animal centrosomes. Centrioles are very large structures (~ 200nm x 400nm), but their basic framework is apparently composed of relatively few protein types. We are studying how these protein components come together during centriole duplication.

The group uses NMR, X-ray crystallography and biophysics in equal measures, and we have access to excellent facilities for all techniques in the department. We collaborate locally and internationally with groups doing microscopy, tomography and molecular biology.
Key Publications

Kitagawa D et al. (2011)
Structural basis of the 9-fold symmetry of centrioles. Cell 144, 364-75

Erat MC et al. (2010)
Implications for collagen binding from the crystallographic structure of fibronectin 6FnI1-2FnII7FnI. J Biol Chem 285, 33764-70

Erat MC et al. (2009)
Identification and structural analysis of type I collagen sites in complex with fibronectin fragments. Proc Natl Acad Sci USA 106, 4195-200. 

Vakonakis I et al. (2007) 
Interdomain association in fibronectin: insight into cryptic sites and fibrillogenesis. EMBO J 26, 2575-83