title: Hinge bending within the cytokine receptor superfamily revealed by the 2.4 A crystal structure of the extracellular domain of rabbit tissue factor.
abstract: Tissue factor (TF), a member of the cytokine receptor superfamily, is the obligate cofactor of coagulation factor VIIa (FVIIa), and has a pivotal role in initiating the extrinsic pathway of blood coagulation through formation of the TF x FVIIa complex. The crystal structure of the extracellular portion of rabbit TF has been solved at 2.35 A resolution and refined to a crystallographic R-value of 19.1% (free R-value, 27.7%). Like the human homologue, the extracellular portion consists of two fibronectin type III domains connected by a short alpha-helical segment. Unexpectedly, the two molecules in the crystallographic asymmetric unit differ in their relative domain-domain orientation, revealing unsuspected hinge motion consisting of a rotation of about 12.7 degrees around an axis intersecting the linker segment at residue 106. Superposition of rabbit tissue factor with free and bound human tissue factor allows for the detection of an identical, albeit smaller, hinge motion in human TF induced upon binding of FVIIa. This raises the possibility that a very similar hinge axis may be present in other members of the cytokine receptor superfamily.
authors.affiliation: Forschungsgruppe Kristallographie, Max-Delbrück-Centrum für Molekulare Medizin, Berlin-Buch, Germany. yam@mdc-berlin.de
authors.forename: Y A
authors.initials: YA
authors.lastname: Muller
authors.forename: R F
authors.initials: RF
authors.lastname: Kelley
authors.forename: A M
authors.initials: AM
authors.lastname: de Vos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D015942:Factor VIIa / Q000378:metabolism; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011817:Rabbits; D018121:Receptors, Cytokine / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D013925:Thromboplastin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D018121:Receptors, Cytokine; D013925:Thromboplastin; D015942:Factor VIIa