There are two forms of Neuropilins, NRP-1 and NRP-2. They are transmembrane glycoproteins, and predominantly co-receptors for another class of proteins known as semaphorins. Of the semaphorins, NRP-1 and NRP-2 are specifically receptors for class-3 semaphorins, which, amongst many things, are responsible for axon guidance during the development of the nervous system in vertebrates.
Neuropilins work as co-receptors as they have a very small cytoplasmic domain and thus rely upon other molecules to transduce their signals across a cell membrane, normally plexins. Neuropilins generally work as dimers and different combinations have different affinities for molecules. For example, NRP-1 homodimers have high affinity for Sema-3A, whilst NRP-2 homodimers have high affinity for Sema-3F.
Another ligand for neuropilins is VEGF, a growth factor involved in the regulation of angiogenesis.
Neuropilin-1 is a therapeutic target protein in the treatment for leukemia and lymphoma, since It has been shown that there is increased expression in neuropilin-1 in leukemia and lymphoma cell lines. Also, antagonism of neuropilin-1 has been found to inhibit tumour cell migration and adhesion.
The structure of B1 domain (coagulation factor 5/8 type) of neuropilin-1 was determined through X-Ray Diffraction with a resolution of 2.90 Å. The secondary structure of this domain is 5% alpha helical and 46% beta sheet.
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