Iain Campbell
Integrin adhesion complexes and fibronectin
Co-workers: Dr Jonathan Boyd; Dr Michèle Erat; Dr Roman Bonet Figueredo; Dr Anna K. Füzéry; Christina Mayer; Maria Reichenbach; Nick Soffe
The group is interested in the structure and interactions of modular proteins that are involved in a variety of cell adhesion and signalling events. Of particular interest are the proteins involved in the formation of integrin adhesions - dynamic assemblies of modular proteins that form and dissolve as cells migrate (see e.g. http://www.cellmigration.org).
Proteins currently being studied include fibronectin, integrins, talin, focal adhesion kinase, parvin, filamin and paxillin. Fibronectin interacts with other extracellular matrix proteins, such as collagen, as well as the key cell surface adhesion receptors, integrins. The adhesion properties of integrins are controlled by various intracellular proteins and their phosphorylation state. Talin is known to be especially important for integrin activation.
Our goal is to understand how the assembly of these various proteins are regulated. Unstructured regions of these proteins are often involved in regulation by phosphorylation. We work closely with other members of the Department and several international collaborators.
The general strategy we use is one of 'dissection', where selected regions of proteins are expressed and characterised, their structure determined and their binding sites defined by NMR and/ or other biophysical methods. The group uses NMR as its major tool and has access to excellent facilities with 500 MHz (2), 600 MHz (2), 750 MHz and 950 MHz spectrometers.
Publications
- Wegener KL, et al. Structural basis of talin activation of integrins (2007) Cell 128, 171-182
- Campbell ID. Structure of the living cell (Croonian lecture) Phil Trans Roy Soc 363, 2379-91
- Lad Y, Jiang P, Ruskamo S, Harburger DS, Ylanne J, Campbell ID & Calderwood DA. Structural basis of the migfilin-filamin interaction and competition with integrin β tails (2008) J Biol Chem 283 35154-63
- Anthis NJ, Wegener KL, Ye F, Kim C, Goult BT, Lowe ED, Vakonakis I, Bates N, Critchley DR, Ginsberg MH, Campbell ID. The structure of an integrin/talin complex reveals the basis of inside-out signal transduction (2009) EMBO J. 28 3623-32
- Anthis NJ, Haling JR, Oxley CL, Memo M, Wegener KL, Lim CJ, Ginsberg MH, Campbell ID. Beta integrin tyrosine phosphorylation is a conserved mechanism for regulating talin-induced integrin activation (2009) J Biol Chem. 284 36700-10
More Publications...
Research Images
Figure 1: Integrins are heterodimeric cell surface receptors that can be activated (with increased affinity) both from inside and from outside the cell. The key intracellular activator is talin. We have recently proposed (EMBO J 28:3623-32, 2009) an activation mechanism that involves talin binding to the beta integrin cytoplasmic tail (red) and two of the talin head domains (F2 and F3). The diagram shows integrins in the ‘on’ and ‘off’ states, talin and, in expanded form, the structure of the complex of the talin head fragment with the β-tail and its membrane-spanning helix
Contact: iain.campbell@bioch.ox.ac.uk
Graduate Student and Postdoctoral Positions: No positions currently available
Website: http://www2.bioch.ox.ac.uk/~rrnmr