αV β3 is a type of integrin that is a receptor for vitronectin .[1] It consists of two components, integrin alpha V and integrin beta 3 (CD 61), and is expressed by platelets . Furthermore, it is a receptor for phagocytosis on macrophages or dendritic cells .[2]
Integrin αV β3 is a potential drug target because abnormal expression of v3 is linked to the development and progression of various diseases. Its role in angiogenesis , in cancer and other diseases, is linked to the blood supply for problematic overgrowths.[3]
Inhibitors like etaracizumab may be used as antiangiogenics .[4]
One novel protein (ProAgio) has been designed to bind at an unusual site, and then induces apoptosis by recruiting caspase 8 .[3] It is designed by mutating domain 1 of CD2 (D1-CD2), which naturally binds weakly to the receptor.[5]
Fibronectin domain 10 contains the RGD motif that αV β3 recognizes. A high-affinity, pure antagonist mutant has been discovered for this protein.[6]
^ Hermann P, Armant M, Brown E, Rubio M, Ishihara H, Ulrich D, Caspary RG, Lindberg FP, Armitage R, Maliszewski C, Delespesse G, Sarfati M (February 1999). "The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23" . The Journal of Cell Biology . 144 (4): 767–75. doi :10.1083/jcb.144.4.767 . PMC 2132927 . PMID 10037797 .
^ Yamaguchi H, Takagi J, Miyamae T, Yokota S, Fujimoto T, Nakamura S, Ohshima S, Naka T, Nagata S (May 2008). "Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosus" . Journal of Leukocyte Biology . 83 (5): 1300–7. doi :10.1189/jlb.1107730 . PMID 18303131 .
^ a b Novel Protein Agent Targets Cancer and Host of Other Diseases. June 2016
^ Santulli G, Basilicata MF, De Simone M, Del Giudice C, Anastasio A, Sorriento D, Saviano M, Del Gatto A, Trimarco B, Pedone C, Zaccaro L, Iaccarino G (January 2011). "Evaluation of the anti-angiogenic properties of the new selective αVβ3 integrin antagonist RGDechiHCit" . Journal of Translational Medicine . 9 (1): 7. doi :10.1186/1479-5876-9-7 . PMC 3027097 . PMID 21232121 .
^ Turaga, Ravi Chakra; Yin, Lu; Yang, Jenny J.; Lee, Hsiauwei; Ivanov, Ivaylo; Yan, Chunli; Yang, Hua; Grossniklaus, Hans E.; Wang, Siming; Ma, Cheng; Sun, Li; Liu, Zhi-Ren (31 May 2016). "Rational design of a protein that binds integrin αvβ3 outside the ligand binding site" . Nature Communications . 7 (1): 11675. Bibcode :2016NatCo...711675T . doi :10.1038/ncomms11675 . PMC 4895024 . PMID 27241473 .
^ Van Agthoven JF, Xiong JP, Alonso JL, Rui X, Adair BD, Goodman SL, Arnaout MA (April 2014). "Structural basis for pure antagonism of integrin αVβ3 by a high-affinity form of fibronectin" . Nature Structural & Molecular Biology . 21 (4): 383–8. doi :10.1038/nsmb.2797 . PMC 4012256 . PMID 24658351 .
Alpha Beta Dimers
Cytoadhesin receptor: Fibrinogen receptor: Fibronectin receptor: Leukocyte-adhesion receptor: Very late antigen receptor:
Integrin alpha1beta1
Integrin alpha2beta1
Integrin alpha3beta1
VLA-4
Alpha-5 beta-1
Integrin alpha6beta1
Vitronectin receptor: