Kurata H, Cheng H M, Kozutsumi Y, Yokota Y, Kawasaki T
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Biochem Biophys Res Commun. 1993 Mar 31;191(3):1204-10. doi: 10.1006/bbrc.1993.1345.
Human mannan-binding protein (MBP) is a C-type serum lectin involved in an immunoglobulin-independent host defense. Recently, a common defect of immune opsonin was found to be associated with very low serum levels of MBP. This deficiency was thought to be an effect of a single base substitution in the MBP gene, which resulted in the conversion of Gly54 to Asp. In this study, three mutant MBPs were expressed in COS-1 cells and the effects of these mutations were studied. Gly54Asp-MBP and Gly57Asp-MBP were secreted into the medium almost at the same levels as the wild type MBP, but the formation of higher multimers and the activation of complement were interfered with significantly. The other mutant, in which Leu was inserted into the Gly63-Gln-Gly sequence to restore the collagen motif of the Gly-Xaa-Yaa repeat, was secreted at levels similar to that of the wild type, formed higher multimers and activated complement in a manner not significantly altered from that of the wild type. These results are discussed with regard to the molecular basis of patients with opsonic defects.
人甘露聚糖结合蛋白（MBP）是一种参与非免疫球蛋白依赖的宿主防御的C型血清凝集素。最近，发现免疫调理素的一种常见缺陷与血清MBP水平极低有关。这种缺陷被认为是MBP基因中单个碱基取代的结果，该取代导致Gly54转变为Asp。在本研究中，三种突变型MBP在COS-1细胞中表达，并研究了这些突变的影响。Gly54Asp-MBP和Gly57Asp-MBP分泌到培养基中的水平几乎与野生型MBP相同，但更高聚体的形成和补体的激活受到显著干扰。另一种突变体是在Gly63-Gln-Gly序列中插入Leu以恢复Gly-Xaa-Yaa重复序列的胶原基序，其分泌水平与野生型相似，形成更高聚体并以与野生型无显著差异的方式激活补体。针对调理缺陷患者的分子基础对这些结果进行了讨论。
