MRC National Institute for Medical Research, London
Science for Health
Martin Webb group project:
The role of small G proteins in cell signalling
Small G proteins share a number of features with motor proteins, in that they use the energy of GTP hydrolysis to modulate protein-protein interactions, but in these cases typically act as molecular switches.
The role of two small G proteins, Rac and Ras, in their signalling pathways is being investigated by probing their molecular interactions with effectors and regulators. We are aiming to understand how such protein-protein interactions are modulated to produce control and the appropriate time frame of responses. They are studied using physical, biochemical and structural approaches, particularly fluorescence and kinetics. In addition we are probing how the activation/deactivation cycle of the small G proteins is brought about by extrinsic protein factors.
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The picture shows the fluorescence change of a coumarin-labeled GDI (a modulator of rho family activity) on interaction with Rac.GDP (Blue without Rac, yellow with Rac bound). This can be used as a sensor for Rac and for probing the interactions between Rac and GDI.
Selected publications
- Phillips, R. A., Hunter, J. L., Eccleston, J. F., and Webb, M. R. (2003)
The mechanism of Ras GTPase activation by neurofibromin.
Biochemistry 42, 3956 - 3965 - Shutes, A., Phillips, R. A., Corrie, J. E. T., and Webb, M. R. (2002)
The role of magnesium in nucleotide exchange on the small G protein Rac, investigated using novel fluorescent guanine nucleotide analogues.
Biochemistry 41, 3828-3835 - Newcombe, A. R., Stockley, R. W., Hunter, J. L., and Webb, M. R. (1999)
The interaction between Rac1 and its guanine nucleotide dissociation inhibitor (GDI), monitored by a single fluorescent coumarin attached to GDI.
Biochemistry 38, 6879-6886 - Nixon, A. E., Brune, M., Lowe, P. N., and Webb, M. R. (1995)
Kinetics of inorganic phosphate release during the interaction of p21ras with the GTPase activating proteins, p120-GAP and neurofibromin.
Biochemistry 34, 15592-15598
Webb group
Recent publications
Research projects
- DNA helicases: mechanism of coupling ATP hydrolysis to DNA translocation
- Myosins: the relationship between ATP hydrolysis and mechanical events
- Development of fluorescent biosensors and other probes
- The role of small G proteins in cell signalling
Expertise/techniques
Webb biography
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