1IQD

Human Factor VIII C2 Domain complexed to human monoclonal BO2C11 Fab.

Summary for 1IQD

• Entry DOI: 10.2210/pdb1iqd/pdb
• Related: 1D7P
• Descriptor: HUMAN MONOCLONAL BO2C11 FAB LIGHT CHAIN, HUMAN MONOCLONAL BO2C11 FAB HEAVY CHAIN, HUMAN FACTOR VIII, ... (4 entities in total)
• Functional Keywords: factor viii, c2 domain, antibody, blood coagulation, inhibitor, bo2c11, immune system-blood clotting complex, immune system/blood clotting
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted, extracellular space: P00451
• Total number of polymer chains: 3
• Total formula weight: 63403.13

Authors

Spiegel Jr., P.C.,Jacquemin, M.,Saint-Remy, J.M.,Stoddard, B.L.,Pratt, K.P. (deposition date: 2001-07-21, release date: 2001-08-15, Last modification date: 2024-10-30)

Primary citation

Spiegel Jr., P.C.,Jacquemin, M.,Saint-Remy, J.M.,Stoddard, B.L.,Pratt, K.P.
Structure of a factor VIII C2 domain-immunoglobulin G4kappa Fab complex: identification of an inhibitory antibody epitope on the surface of factor VIII.
Blood, 98:13-19, 2001

PubMed Abstract: The development of an immune response to infused factor VIII is a complication affecting many patients with hemophilia A. Inhibitor antibodies bind to antigenic determinants on the factor VIII molecule and block its procoagulant activity. A patient-derived inhibitory immunoglobulin G4kappa antibody (BO2C11) produced by an immortalized memory B-lymphocyte cell line interferes with the binding of factor VIII to phospholipid surfaces and to von Willebrand factor. The structure of a Fab fragment derived from this antibody complexed with the factor VIII C2 domain was determined at 2.0 A resolution. The Fab interacts with solvent-exposed basic and hydrophobic side chains that form a membrane-association surface of factor VIII. This atomic resolution structure suggests a variety of amino acid substitutions in the C2 domain of factor VIII that might prevent the binding of anti-C2 inhibitor antibodies without significantly compromising the procoagulant functions of factor VIII.

PubMed: 11418455
DOI: 10.1182/blood.V98.1.13

Experimental method

X-RAY DIFFRACTION (2 Å)