scholarly journals Inhibition of Plasma Coagulation through Interaction between Oxidized Low-Density Lipoprotein and Blood Coagulation Factor VIII

2005 ◽  
Vol 28 (6) ◽  
pp. 952-956 ◽  
Author(s):  
Takeshi Kumagai ◽  
Yukari Hoshi ◽  
Hiromu Tsutsumi ◽  
Keiichi Ebina ◽  
Katsushi Yokota
Keyword(s):  
Factor Viii ◽  
Blood Coagulation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Plasma Coagulation ◽  
Blood Coagulation Factor Viii

Characterization of Molecular Interaction of Blood Coagulation Factor VIII and Its Clearance Receptor, Low-Density Lipoprotein Receptor.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2206-2206
Author(s):  
James H Kurasawa ◽  
Svetlana A Shestopal ◽  
Elena Karnaukhova ◽  
Evi B Struble ◽  
Timothy K Lee ◽  
...  
Keyword(s):  
Factor Viii ◽  
Blood Coagulation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coagulation Factor ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
Clearance Receptor ◽  
Blood Coagulation Factor Viii

Abstract Abstract 2206 Background. Clearance of blood coagulation factor VIII (FVIII) is mediated by several receptors (Saenko E. et al, 1999; Lenting P. et al, 1999 and Sarafanov A. et al, 2001) and one of them was proposed to be low-density lipoprotein receptor (LDLR) (Bovenschen N. et al, 2005). Besides FVIII, the major ligands of LDLR are plasma lipoproteins. The ligand-binding portion of LDLR is represented by a cluster of seven complement-type repeats. Each repeat forms a structurally autonomous domain, which are connected with flexible linkers. Two and five adjacent CRs were shown to form sites for the lipoproteins ApoE and ApoB, respectively, and the site for FVIII has not been determined. Objective. As a part of elucidation of mechanisms of FVIII clearance, our goal was to identify the FVIII-binding region on LDLR. Experimental Approach. Our experimental strategy was based on generation of recombinant CR-doublets that systematically overlap the CR cluster in LDLR (Fig. 1) and testing their interactions with FVIII. The proteins were expressed in insect cells using a baculovirus system and tested for structural integrity by circular dichroism. The functional properties of the fragments were assessed by their binding with alpha-2-macroglobulin receptor-associated protein (RAP), a universal ligand of a family of receptors that LDLR belongs to. The binding studies were performed using surface plasmon resonance technique. Using this assay, the LDLR fragments were further tested for interaction with different FVIII preparations, such as plasma-derived FVIII and recombinant FVIII: Advate (full-size FVIII) and Xyntha (B-domain deleted FVIII). The specificity of these interactions was tested in a competitive binding assay using an anti-FVIII single-chain variable antibody fragment KM33 known to inhibit binding FVIII to LDLR (Limburg V. et al, 2005). Also, the specificity of the interaction of LDLR fragments and FVIII was tested upon mutating the fragments by targeting conservative tryptophanes, one residue per selected CR. Upon expressing the mutants, their structural adequacy to the respective wild-type forms was confirmed by circular dichroism. Results. Three overlapping CR doublets were found active for binding with all FVIII preparations (Fig. 2). In presence of increased concentrations of KM33 and upon site-directed mutagenesis of the LDLR fragments, this binding was diminished confirming its specificity. Conclusions. The binding site of LDLR for FVIII is formed by a region spanned by the complement-type repeats from second to fifth. We proposed a tentative model of the interaction (Fig. 3), in which this region of the receptor contacts the A3 and C1 domains of FVIII. These portions of FVIII were previously shown to be involved in interaction with another FVIII clearance receptor known as LDLR-related protein (Bovenschen N. et al, 2003 and Meems H. et al, 2011). Disclosures: No relevant conflicts of interest to declare.

scholarly journals Mapping the Binding Region on the Low Density Lipoprotein Receptor for Blood Coagulation Factor VIII

2013 ◽  
Vol 288 (30) ◽  
pp. 22033-22041 ◽  
Author(s):  
James H. Kurasawa ◽  
Svetlana A. Shestopal ◽  
Elena Karnaukhova ◽  
Evi B. Struble ◽  
Timothy K. Lee ◽  
...  
Keyword(s):  
Factor Viii ◽  
Blood Coagulation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coagulation Factor ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Binding Region ◽  
Density Lipoprotein Receptor ◽  
Blood Coagulation Factor Viii

Cluster III of Low-Density Lipoprotein Receptor-Related Protein 1 Binds Activated Blood Coagulation Factor VIII

Biochemistry ◽  
2014 ◽  
Vol 54 (2) ◽  
pp. 481-489 ◽  
Author(s):  
James H. Kurasawa ◽  
Svetlana A. Shestopal ◽  
Samuel A. Woodle ◽  
Mikhail V. Ovanesov ◽  
Timothy K. Lee ◽  
...  
Keyword(s):  
Factor Viii ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coagulation Factor ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Related Protein ◽  
Density Lipoprotein Receptor ◽  
Lipoprotein Receptor Related Protein ◽  
Blood Coagulation Factor Viii

scholarly journals The 3.2 Å structure of a bioengineered variant of blood coagulation factor VIII indicates two conformations of the C2 domain

2019 ◽  
Vol 18 (1) ◽  
pp. 57-69 ◽  
Author(s):  
Ian W. Smith ◽  
Anne E. d'Aquino ◽  
Christopher W. Coyle ◽  
Andrew Fedanov ◽  
Ernest T. Parker ◽  
...  
Keyword(s):  
Factor Viii ◽  
Blood Coagulation ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
C2 Domain ◽  
Blood Coagulation Factor Viii

Changes in the Factor VIII C2 domain upon membrane binding determined by hydrogen–deuterium exchange MS

2014 ◽  
Vol 461 (3) ◽  
pp. 443-451 ◽  
Author(s):  
Dionysios Pantazatos ◽  
Christopher R. Gessner ◽  
Virgil L. Woods ◽  
Gary E. Gilbert
Keyword(s):  
Factor Viii ◽  
Blood Coagulation ◽  
Membrane Binding ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Hydrogen Deuterium Exchange ◽  
Factor Ixa ◽  
Hydrogen Deuterium ◽  
Binding Peptides ◽  
Blood Coagulation Factor Viii

Blood coagulation Factor VIII binds to a membrane in order to function as a cofactor for Factor IXa, preventing haemophilia. The present study indicates that membrane-binding peptides of Factor VIII are largely protected from water exposure, indicating that they become immersed in the membrane.

scholarly journals Limited Promiscuity of HLA-DRB1 Presented Peptides Derived of Blood Coagulation Factor VIII

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80239 ◽  
Author(s):  
Simon D. van Haren ◽  
Aleksandra Wroblewska ◽  
Eszter Herczenik ◽  
Paul H. Kaijen ◽  
Aleksandra Ruminska ◽  
...  
Keyword(s):  
Factor Viii ◽  
Blood Coagulation ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Blood Coagulation Factor Viii
Sign in / Sign up

Export Citation Format

Share Document