Crystallization and preliminary X-ray diffraction analysis of the complex between a human anti-interferon antibody fragment and human interferon alpha-2A.
Recombinant human interferon alpha-2A (rhIFN-alpha-2A) has been crystallized in complex with the recombinantly produced Fab fragment of a therapeutic monoclonal antibody (MEDI545; IgG1/kappa) which targets several human interferon alpha subtypes. This constitutes the first reported crystals of a human type I interferon bound to an antibody. The orthorhombic crystals belonged to either space group I222 or I2(1)2(1)2(1), with unit-cell parameters a = 134.82, b = 153.26, c = 163.49 A. The diffraction of the crystals extended to 3.0 A resolution. The asymmetric unit contained two Fab-rhIFN-alpha-2A complexes. This corresponded to a crystal volume per protein weight (V(M)) of 3.02 A(3) Da(-1) and a solvent content of 59.3%. The corresponding three-dimensional structure is expected to shed light on the mechanism of action of MEDI545 and the molecular basis of its specificity.
Oganesyan
Vaheh
V
Department of Antibody Discovery and Protein Engineering, Gaithersburg, MD 20878, USA.
Damschroder
Melissa M
MM
Cook
Kimberly E
KE
Wu
Herren
H
Dall'Acqua
William F
WF
D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry*; D000911:Antibodies, Monoclonal / Q000737:chemistry; D003460:Crystallization; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D021621:Imaging, Three-Dimensional; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000737:chemistry*; D007372:Interferons / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D011994:Recombinant Proteins; D014961:X-Ray Diffraction
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D007372:Interferons