人抗干扰素抗体片段与人干扰素α-2A复合物的结晶及初步X射线衍射分析
Crystallization and preliminary X-ray diffraction analysis of the complex between a human anti-interferon antibody fragment and human interferon alpha-2A.
作者信息
Oganesyan Vaheh, Damschroder Melissa M, Cook Kimberly E, Wu Herren, Dall'Acqua William F
机构信息
Department of Antibody Discovery and Protein Engineering, Gaithersburg, MD 20878, USA.
出版信息
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Jan 1;65(Pt 1):14-6. doi: 10.1107/S1744309108037925. Epub 2008 Dec 25.
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.
重组人干扰素α-2A（rhIFN-α-2A）已与靶向多种人干扰素α亚型的治疗性单克隆抗体（MEDI545；IgG1/κ）的重组产生的Fab片段形成复合物结晶。这是首次报道的人I型干扰素与抗体结合的晶体。正交晶体属于空间群I222或I2(1)2(1)2(1)，晶胞参数a = 134.82，b = 153.26，c = 163.49 Å。晶体的衍射延伸至3.0 Å分辨率。不对称单元包含两个Fab-rhIFN-α-2A复合物。这对应于每蛋白质重量的晶体体积（V(M)）为3.02 Å(3) Da(-1)，溶剂含量为59.3%。相应的三维结构有望阐明MEDI545的作用机制及其特异性的分子基础。
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