|Locus||Chr. 10 p12|
|Locus||Chr. 2 q34|
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, among 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 (normally plexins) to transduce their signals across a cell membrane. Neuropilins generally work as dimers and different combinations have different affinities for molecules. For example, NRP-1 homodimers have high affinity for Sema3A, whilst NRP-2 homodimers have high affinity for Sema3F. 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.
Neuropilins contain the following four domains:
- N-terminal CUB domain (for complement C1r/C1s, Uegf, Bmp1)
- Coagulation factor 5/8 type, C-terminal (discoidin domain)
- MAM domain (for meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu)
- C-terminal neuropilin
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.
- "Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction". J. Med. Chem. 53 (5): 2215–26. PMC . PMID 20151671. doi:10.1021/jm901755g.; Jarvis A, Allerston CK, Jia H, Herzog B, Garza-Garcia A, Winfield N, Ellard K, Aqil R, Lynch R, Chapman C, Hartzoulakis B, Nally J, Stewart M, Cheng L, Menon M, Tickner M, Djordjevic S, Driscoll PC, Zachary I, Selwood DL (March 2010).
- Mecollari, V; Nieuwenhuis, B; Verhaagen, J (2014). "A perspective on the role of class III semaphorin signaling in central nervous system trauma". Frontiers in Cellular Neuroscience. 8: 328. PMC . PMID 25386118. doi:10.3389/fncel.2014.00328.
- Karjalainen K, Jaalouk DE, Bueso-Ramos CE, Zurita AJ, Kuniyasu A, Eckhardt BL, Marini FC, Lichtiger B, O'Brien S, Kantarjian HM, Cortes JE, Koivunen E, Arap W, Pasqualini R (November 2010). "Targeting neuropilin-1 in human leukemia and lymphoma". Blood. 117 (3): 920–927. PMC . PMID 21063027. doi:10.1182/blood-2010-05-282921.
- Jia H, Cheng L, Tickner M, Bagherzadeh A, Selwood D, Zachary I (February 2010). "Neuropilin-1 antagonism in human carcinoma cells inhibits migration and enhances chemosensitivity". Br. J. Cancer. 102 (3): 541–52. PMC . PMID 20087344. doi:10.1038/sj.bjc.6605539.
- "MolProbity Ramachandran analysis of PDB structure 3I97" (PDF). www.pdb.org.