Alpha-v beta-3 explained

αVβ3 is a type of integrin that is a receptor for vitronectin.[1] It consists of two components, integrin alpha V and integrin beta 3 (CD61), and is expressed by platelets. Furthermore, it is a receptor for phagocytosis on macrophages or dendritic cells.[2]

As a drug target

Integrin αVβ3 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 αVβ3 recognizes. A high-affinity, pure antagonist mutant has been discovered for this protein.[6]

See also

Notes and References

  1. Hermann P, Armant M, Brown E, Rubio M, Ishihara H, Ulrich D, Caspary RG, Lindberg FP, Armitage R, Maliszewski C, Delespesse G, Sarfati M . 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 . February 1999 . 10037797 . 2132927 . 10.1083/jcb.144.4.767 .
  2. Yamaguchi H, Takagi J, Miyamae T, Yokota S, Fujimoto T, Nakamura S, Ohshima S, Naka T, Nagata S . Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosus . Journal of Leukocyte Biology . 83 . 5 . 1300–7 . May 2008 . 18303131 . 10.1189/jlb.1107730 . free .
  3. http://www.genengnews.com/gen-news-highlights/new-protein-agent-targets-cancer-and-host-of-other-diseases/81252780/ Novel Protein Agent Targets Cancer and Host of Other Diseases. June 2016
  4. 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 . Evaluation of the anti-angiogenic properties of the new selective αVβ3 integrin antagonist RGDechiHCit . Journal of Translational Medicine . 9 . 1 . 7 . January 2011 . 21232121 . 3027097 . 10.1186/1479-5876-9-7 . free .
  5. 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 . Rational design of a protein that binds integrin αvβ3 outside the ligand binding site . Nature Communications . 31 May 2016 . 7 . 1 . 10.1038/ncomms11675 . free . 27241473 . 4895024 . 11675. 2016NatCo...711675T .
  6. Van Agthoven . JF . Xiong . JP . Alonso . JL . Rui . X . Adair . BD . Goodman . SL . Arnaout . MA . vanc. Structural basis for pure antagonism of integrin αVβ3 by a high-affinity form of fibronectin. . Nature Structural & Molecular Biology . April 2014 . 21 . 4 . 383–8 . 10.1038/nsmb.2797 . 24658351 . 4012256.

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