Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex
作者： Jacky Chi Ki Ngo , Mingdong Huang , David A. Roth , Barbara C. Furie , Bruce Furie
DOI: 10.1016/J.STR.2008.03.001
关键词: Factor IXa 、 Binding site 、 Coagulation 、 Stereochemistry 、 Membrane 、 Factor IXa-factor VIIIa 、 Protein structure 、 Crystal structure 、 Chemistry 、 Immunoglobulin light chain
摘要: Factor VIII is a procofactor that plays critical role in blood coagulation, and missing or defective hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein composed five globular domains contains one Ca(2+) two Cu(2+) ions. The three homologous A form triangular heterotrimer where A1 A3 serve as base interact with C2 C1 domains, respectively. structurally reveal membrane binding features. Based on biochemical studies, model IXa-factor VIIIa complex was constructed by silico docking. IXa wraps across side VIII, an extended interface spans heavy light chains. provides insight into activation interaction surface.
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V.P. Mutucumarana, E.J. Duffy, P Lollar, A.E. Johnson, The active site of factor IXa is located far above the membrane surface and its conformation is altered upon association with factor VIIIa. A fluorescence study. Journal of Biological Chemistry. ,vol. 267, pp. 17012- 17021 ,(1992) , 10.1016/S0021-9258(18)41886-8
P J Fay, C F Huggins, T Beattie, L M Regan, Factor VIIIa A2 subunit residues 558-565 represent a factor IXa interactive site. Journal of Biological Chemistry. ,vol. 269, pp. 20522- 20527 ,(1994) , 10.1016/S0021-9258(17)32024-0
M E Nesheim, K G Mann, Thrombin-catalyzed activation of single chain bovine factor V. Journal of Biological Chemistry. ,vol. 254, pp. 1326- 1334 ,(1979) , 10.1016/S0021-9258(17)34206-0
E.J. Duffy, E.T. Parker, V.P. Mutucumarana, A.E. Johnson, P Lollar, Binding of factor VIIIa and factor VIII to factor IXa on phospholipid vesicles. Journal of Biological Chemistry. ,vol. 267, pp. 17006- 17011 ,(1992) , 10.1016/S0021-9258(18)41885-6
Zbyszek Otwinowski, Wladek Minor, Processing of X-ray diffraction data collected in oscillation mode Methods in Enzymology. ,vol. 276, pp. 307- 326 ,(1997) , 10.1016/S0076-6879(97)76066-X
H Nishimura, H Takeya, T Miyata, K Suehiro, T Okamura, Y Niho, S Iwanaga, Factor IX Fukuoka. Substitution of ASN92 by His in the second epidermal growth factor-like domain results in defective interaction with factors VIIa/X. Journal of Biological Chemistry. ,vol. 268, pp. 24041- 24046 ,(1993) , 10.1016/S0021-9258(20)80489-X
Peter J. Lenting, Jan-Willem H. P. van de Loo, Marie-José S. H. Donath, Jan A. van Mourik, Koen Mertens, The sequence Glu1811-Lys1818 of human blood coagulation factor VIII comprises a binding site for activated factor IX. Journal of Biological Chemistry. ,vol. 271, pp. 1935- 1940 ,(1996) , 10.1074/JBC.271.4.1935
P.E. Hughes, G. Morgan, E.K. Rooney, G.G. Brownlee, P. Handford, Tyrosine 69 of the first epidermal growth factor-like domain of human factor IX is essential for clotting activity Journal of Biological Chemistry. ,vol. 268, pp. 17727- 17733 ,(1993) , 10.1016/S0021-9258(17)46765-2
Darla Liles, Charles N Landen, Dougald M Monroe, Celeste M Lindley, Marjorie s Read, Harold R Roberts, Kenneth M Brinkhous, Extravascular administration of factor IX: potential for replacement therapy of canine and human hemophilia B. Thrombosis and Haemostasis. ,vol. 77, pp. 944- 948 ,(1997) , 10.1055/S-0038-1656082
Kathleen P. Pratt, Betty W. Shen, Kazuya Takeshima, Earl W. Davie, Kazuo Fujikawa, Barry L. Stoddard, Structure of the C2 domain of human factor VIII at 1.5 Å resolution Nature. ,vol. 402, pp. 439- 442 ,(1999) , 10.1038/46601