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Structure of key protein involved in cancer, osteoporosis and foot-and-mouth disease finally solved

Researchers at Massachusetts General Hospital (MGH) have solved the structure of an integrin receptor, a key protein involved in diseases and processes ranging from tumor angiogenesis and breast cancer metastasis to osteoporosis, vascular restenosis and foot-and-mouth disease. The finding, which will appear in Science magazine, was published Sept. 6 on the Science Express website http://www.sciencexpress.org.

"Knowing the shape of this receptor will help us all develop strategies to target many of these diseases," says M. Amin Arnaout, MD, Director of the Structural Biology Program at MGH and Chief of the MGH Renal Unit. The other members of the MGH research team are Jian-Ping Xiong, PhD, Thilo Stehle, PhD, and David Scott, MD, PhD. The new information may be useful in designing novel anti-angiogenic, anti-inflammatory, anti-viral, and anti-osteoporosis drugs that target integrins.

The MGH team of researchers has been trying to decipher the three dimensional structure of this particular integrin receptor for several years. "This is the first look anyone has had at the whole structure of this class of receptors," says Arnaout.

Integrin receptors transmit chemical signals from a cell?s surface into its interior, which regulate most cellular processes such as attachment, proliferation, differentiation, and survival. Integrin receptors also have a unique ability to undergo shape-shifting as they become activated in response to the specialized needs of cells. "Elucidating the basic shape of these receptors is therefore key to understanding their function," says Arnaout.

An activated integrin receptor is able to bind a molecule called a ligand, in a lock and key fashion. Integrin receptors are very promiscuous, though, and they fit a variety of ligand 'keys,' including viral proteins that hijack these receptors to gain entry into cells.

There are many different types of integrin rec
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Contact: Susan McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
6-Sep-2001


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