Molecular Insights into Angiogenic Protein

Following up on a report from last year, a study has been published detailing the structure of a key receptor protein, alpha V beta 3, which directs the formation of new blood vessels by binding to other proteins, such as angiostatin and endostatin, produced by rapidly growing tumor cells.

The study, which will appear in a future issue of Science, is being published March 7, 2002, on the Science Express website. The structure of alpha V beta 3 as it interacts with a cyclic peptide was deciphered by scientists at Massachusetts General Hospital (Boston, USA). The research team found that alpha V beta 3 integrin changes its shape when bound to its ligand, allowing it to send chemical signals instructing tumor cells to grow and spread.

"By knowing the intricate molecular interactions between this receptor and its ligand, we are now in a better position to devise inhibitors that block this interaction and therefore prevent or forestall tumor angiogenesis and progression,” says M. Amin Arnaout, M.D., senior author.

There are a further 23 integrin receptors in humans, and some of these play important roles in other diseases such as osteoporosis, stroke, heart attack, diabetes, nephritis and rheumatoid arthritis. All have similar structural motifs, and all bind to their protein ligands in a similar manner. "Catching an integrin in the act of binding to its ligand will offer new means of developing drugs for other debilitating diseases besides cancer,” says Arnaout.




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