Molluscum contagiosum virus interleukin-18 (IL-18) binding protein is secreted as a full-length form that binds cell surface glycosaminoglycans through the C-terminal tail and a furin-cleaved form with only the IL-18 binding domain.
Molluscum contagiosum virus interleukin-18 (IL-18) binding protein is secreted as a full-length form that binds cell surface glycosaminoglycans through the C-terminal tail and a furin-cleaved form with only the IL-18 binding domain.
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传染性软疣病毒白细胞介素 18 (IL-18) 结合蛋白以全长形式分泌，通过 C 末端尾部结合细胞表面糖胺聚糖，以及仅具有 IL-18 结合结构域的弗林蛋白酶切割形式。
DOI：
10.1128/jvi.77.4.2623-2630.2003
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发表时间：
2003
影响因子：
5.4
通讯作者：
Moss,Bernard
中科院分区：
文献类型：
--
作者：
Xiang,Yan;Moss,Bernard
一些痘病毒及其哺乳动物宿主编码以高亲和力结合白细胞介素-18（IL-18）并抑制IL-18介导的免疫应答的同源蛋白。MC 54 L是引起传染性软疣的人痘病毒的IL-18结合蛋白，其独特之处在于具有近100个氨基酸的C-末端尾，其对于IL-18结合是不稳定的。当重组MC 54 L通过C-末端六组氨酸标签表达和纯化时，除了全长蛋白外，还检测到较短的片段。该C-末端片段由MC 54 L被细胞弗林蛋白酶切割而产生，因为当弗林蛋白酶被特异性抑制或当弗林蛋白酶缺陷细胞系用于表达时，该C-末端片段大大减少。此外，通过在体外用弗林蛋白酶切割重组蛋白产生MC 54 L的N-和C-末端片段。弗林蛋白酶切割位点定位在IL-18结合结构域C末端的32个氨基酸片段内。全长MC 54 L，而不是N-末端IL-18结合片段，结合细胞和纯化的肝素和其他糖胺聚糖，这些糖胺聚糖通常存在于细胞表面和细胞外基质中。MC 54 L与肝素结合的Kd值为纳摩尔，同时与IL-18结合。它们不同的糖胺聚糖和细胞结合特性可能允许长和短形式的MC 54 L分别在感染部位附近和更远的位置处抑制IL-18。
Some poxviruses and their mammalian hosts encode homologous proteins that bind interleukin-18 (IL-18) with high affinity and inhibit IL-18-mediated immune responses. MC54L, the IL-18 binding protein of the human poxvirus that causes molluscum contagiosum, is unique in having a C-terminal tail of nearly 100 amino acids that is dispensable for IL-18 binding. When recombinant MC54L was expressed and purified via a C-terminal six-histidine tag, a shorter fragment was detected in addition to the full-length protein. This C-terminal fragment resulted from the cleavage of MC54L by cellular furin, as it was greatly diminished when furin was specifically inhibited or when a furin-deficient cell line was used for expression. Furthermore, the N- and C-terminal fragments of MC54L were generated by cleavage of the recombinant protein with furin in vitro. The furin cleavage site was mapped within a 32-amino-acid segment that is C terminal to the IL-18 binding domain. Full-length MC54L, but not the N-terminal IL-18 binding fragment, bound to cells and to purified heparin and other glycosaminoglycans that are commonly found on the cell surface and in the extracellular matrix. MC54L bound to heparin with a nanomolarKdand could simultaneously bind to IL-18. Their different glycosaminoglycan and cell binding properties may allow the long and short forms of MC54L to inactivate IL-18 near the site of infection and at more distal locations, respectively.