MRC National Institute for Medical Research, London
Science for Health
Structure of key immune protein revealed
09 June 2008
The immune system is the body’s defense system against disease-causing micro-organisms such as viruses, bacteria or fungi. Lymphocytes are white blood cells, which play a critical role in this immune system by producing antibodies and by directly eliminating infected cells.
Most lymphocytes circulate around the body looking for signs of infection. Despite being constantly on the move, patrolling the body, these lymphocytes are in a resting state. However if they encounter an infection they are triggered to divide and they start attacking the invading micro-organism. This activation of the lymphocytes requires signals to be transmitted from the surface of the cell into the nucleus, where genes are then turned on or off.
The Vav1 protein is essential for this signal transmission. In a collaborative study between the Divisions of Immune Cell Biology and Molecular Structure, Dr Jonathan Rapley, Dr Victor Tybulewicz (pictured), and Dr Katrin Rittinger have elucidated the three-dimensional structure of Vav1. This structure has revealed for the first time in molecular detail how this protein performs its function, and this information could be used to rationally design drugs that modulate its activity.
Vav1 has been proposed as a target for drugs to counter auto-immune disorders, where excessive activity of the immune system causes severe disease, for example rheumatoid arthritis or multiple sclerosis. Having drugs that can decrease the activity of Vav1, would be extremely valuable in suppressing the immune response and hence fighting these debilitating diseases. Such drugs may also be useful to suppress the immune response that leads to transplant rejection.
Drs Rittinger and Tybulewicz
Original article
Original articleThe research findings are published in full in:
Jonathan Rapley, Victor L J Tybulewicz & Katrin Rittinger. (2008)
Crucial structural role for the PH and C1 domains of the Vav1 exchange factor
EMBO Reports, epub ahead of print. Abstract
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