title: Factor VIIa and the extracellular domains of human tissue factor form a compact complex: a study by X-ray and neutron solution scattering.
abstract: The four-domain structure of human factor VIIa and the two-domain structure of tissue factor form a tight complex to initiate blood coagulation. By solution scattering, the mean X-ray and neutron radii of gyration RG (which determine macro-molecular elongation) were found to be 3.25 nm, 2.13 nm and 3.14 nm (+/- 0.13 nm) for factor VIIa, the extracellular region of tissue factor and their complex in that order. The mean cross-sectional radii of gyration RXS were 1.33 nm, 0.56 nm and 1.42 nm (+/- 0.13 nm) in that order. The mean lengths were 10.3 nm, 7.7 nm and 10.2 nm in that order. The data show that, in solution, the free proteins have extended domain structures, and the complex is formed by a compact side-by-side alignment of the two proteins along their long axes. The high binding affinity of tissue factor for factor VIIa may thus be accounted for by the occurrence of many intermolecular contacts in the complex.
authors.affiliation: Department of Biochemistry and Molecular Biology, Royal Free Hospital School of Medicine, London, UK.
authors.forename: A W
authors.initials: AW
authors.lastname: Ashton
authors.forename: G
authors.initials: G
authors.lastname: Kemball-Cook
authors.forename: D J
authors.initials: DJ
authors.lastname: Johnson
authors.forename: D M
authors.initials: DM
authors.lastname: Martin
authors.forename: D P
authors.initials: DP
authors.lastname: O'Brien
authors.forename: E G
authors.initials: EG
authors.lastname: Tuddenham
authors.forename: S J
authors.initials: SJ
authors.lastname: Perkins
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015942:Factor VIIa / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009502:Neutrons; D011487:Protein Conformation; D012542:Scattering, Radiation; D013925:Thromboplastin / Q000737:chemistry / Q000378:metabolism*; D014965:X-Rays
chemical_list: D013925:Thromboplastin; D015942:Factor VIIa