CRYSTAL-STRUCTURE OF THE EXTRACELLULAR REGION OF HUMAN TISSUE FACTOR

TISSUE factor is a cell-surface glycoprotein receptor which initiates the blood coagulation cascade after vessel injury by interacting with blood clotting factor VII/VIIa and which is implicated in various path ological processes(1). When bound to tissue factor, factor VII is read ily converted to the active protease factor VIIa by trace amounts of f actors Xa, IXa or VIIa. Human tissue factor consists of 263 residues, the first 219 of which comprise the extracellular region(2). We have d etermined the crystal structure of the extracellular region at a resol ution of 2.2 Angstrom. Tissue factor consists of two immunoglobulin-li ke domains associated through an extensive, novel, interdomain interfa ce region. The binding site for factor VII lies at the interface regio n and involves residues from domain 1 and an extended loop (binding 'f inger') of domain 2. This is the first reported structure of a represe ntative of the class 2 cytokine receptor family, which also includes i nterferon-alpha, interferon-gamma (refs 2, 3) and interleukin-10 (ref. 4) receptors.