Degn Søren E, Hansen Annette G, Steffensen Rudi, Jacobsen Christian, Jensenius Jens C, Thiel Steffen
Departments of Medical Microbiology and Immunology, University of Aarhus, Arhus, Denmark.
J Immunol. 2009 Dec 1;183(11):7371-8. doi: 10.4049/jimmunol.0902388. Epub 2009 Nov 16.
Essential effector functions of innate immunity are mediated by complement activation initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL) and the ficolins. We present a novel, phylogenetically conserved protein, MAp44, which is found in human serum at 1.4 microg/ml in Ca(2+)-dependent complexes with the soluble pattern recognition molecules. The affinity for MBL is in the nanomolar range (K(D) = 0.6 nM) as determined by surface plasmon resonance. The first eight exons of the gene for MAp44 encode four domains shared with MBL-associated serine protease (MASP)-1 and MASP-3 (CUB1-EGF-CUB2-CCP1), and a ninth exon encodes C-terminal 17 aa unique to MAp44. mRNA profiling in human tissues shows high expression in the heart. MAp44 competes with MASP-2 for binding to MBL and ficolins, resulting in inhibition of complement activation. Our results add a novel mechanism to those known to control the innate immune system.
甘露聚糖结合凝集素（MBL）和纤维胶凝蛋白。我们提出了一种新的、系统发育保守的蛋白质MAp44，它以1.4微克/毫升的浓度存在于人类血清中，与可溶性模式识别分子形成钙依赖性复合物。通过表面等离子体共振测定，其对MBL的亲和力处于纳摩尔范围（K(D)=0.6纳摩尔）。MAp44基因的前八个外显子编码与MBL相关丝氨酸蛋白酶（MASP）-1和MASP-3共有的四个结构域（CUB1-EGF-CUB2-CCP1），第九个外显子编码MAp44特有的C末端17个氨基酸。人类组织中的mRNA分析显示心脏中高表达。MAp44与MASP-2竞争结合MBL和纤维胶凝蛋白，从而抑制补体激活。我们的结果为已知的控制固有免疫系统的机制增添了一种新机制。
