EphA4 -- the molecular transformer

Oct 23, 2009
The structure of EphA4

(PhysOrg.com) -- EphA4 is a protein which is attached to the surfaces of many types of human cells and plays a role in a wide range of biological processes. EphA4 functions by binding to ephrin ligands, cell surface proteins which sit on opposing cells. The signalling cascades which result from this contact direct cells to move in a particular direction, to the right place in the body. This is critical in the development of the nervous system, and has also been linked with the suppression of melanoma tumours.

There are fourteen Eph and eight ephrin ligands in the human . These are divided into two classes, A and B. Generally receptors and ligands can only bind strongly to others in the same class, i.e. a class A receptor will bind to a class A ligand. However, this is not always the case, and one receptor in particular, Eph4A, has been known to bind to both class A and B ephrins.

Researchers from the University of Oxford have been studying the EphA4 receptor because it has the potential to be a target in the treatment of cancer. To realise this potential it is necessary to understand the mechanisms by which EphA4 binds to both class A and B ephrins on the molecular scale. They looked at the structure of EphA4 alone, and when bound to both class A and class B ephrins.

They found that when EphA4 is bound to a class A ephrin, it has a shape similar to other class A receptors, but when binding to a class B ephrin it actually changes its shape to resemble other class B receptors. This research has been published in the journal Structure.

“Our results show that EphA4 is a molecular transformer, able to change its shape depending on the that it wants to bind. This explains how, at an , it is able to bind to both classes of ephrins. This is important in understanding how the nervous system develops, and also has potential as a future target for cancer treatments,” said Dr Thomas Bowden, University of Oxford.

More information: Structural Plasticity of Eph Receptor A4 Facilitates Cross-Class Ephrin Signaling Thomas A. Bowden, A. Radu Aricescu, Joanne E. Nettleship, Christian Siebold, Nahid Rahman-Huq, Raymond J. Owens, David I. Stuart and E. Yvonne Jones, Structure, 17 (10), 1386-1397, October 2009, doi:10.1016/j.str.2009.07.018

Provided by Diamond Light Source

Explore further: A refined approach to proteins at low resolution

add to favorites email to friend print save as pdf

Related Stories

Sharing the road

Apr 10, 2008

Come summer, we will once again marvel at the amazing athletic skills of Olympic athletes while in fact, the simple act of walking is no less remarkable. Just to prevent us from toppling over, the neuromuscular ...

Star-shaped cells in the brain aid with learning

Sep 07, 2009

(PhysOrg.com) -- Every movement and every thought requires the passing of specific information between networks of nerve cells. To improve a skill or to learn something new entails more efficient or a greater ...

A molecule keeps anxiety down

Aug 19, 2008

(PhysOrg.com) -- The link between emotions and experiences determines many aspects of our daily life. It allows us to recognize pretty objects or harmful situations. These links are created when nerve cells ...

Recommended for you

A refined approach to proteins at low resolution

Sep 19, 2014

Membrane proteins and large protein complexes are notoriously difficult to study with X-ray crystallography, not least because they are often very difficult, if not impossible, to crystallize, but also because ...

Base-pairing protects DNA from UV damage

Sep 19, 2014

Ludwig Maximilian University of Munich researchers have discovered a further function of the base-pairing that holds the two strands of the DNA double helix together: it plays a crucial role in protecting ...

Smartgels are thicker than water

Sep 19, 2014

Transforming substances from liquids into gels plays an important role across many industries, including cosmetics, medicine, and energy. But the transformation process, called gelation, where manufacturers ...

Separation of para and ortho water

Sep 18, 2014

(Phys.org) —Not all water is equal—at least not at the molecular level. There are two versions of the water molecule, para and ortho water, in which the spin states of the hydrogen nuclei are different. ...

User comments : 0