Graduate School of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Japan.
Department of Life Sciences, University of Trieste, Italy.
FEBS J. 2020 Jun;287(12):2612-2630. doi: 10.1111/febs.15154. Epub 2019 Dec 24.
A 15-kDa lectin, termed SeviL, was isolated from Mytilisepta virgata (purplish bifurcate mussel). SeviL forms a noncovalent dimer that binds strongly to ganglio-series GM1b oligosaccharide (Neu5Acɑ2-3Galβ1-3GalNAcβ1-4Galβ1-4Glc) and its precursor, asialo-GM1 (Galβ1-3GalNAcβ1-4Galβ1-4Glc). SeviL also interacts weakly with the glycan moiety of SSEA-4 hexaose (Neu5Acα2-3Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc). A partial protein sequence of the lectin was determined by mass spectrometry, and the complete sequence was identified from transcriptomic analysis. SeviL, consisting of 129 amino acids, was classified as an R(icin B)-type lectin, based on the presence of the QxW motif characteristic of this fold. SeviL mRNA is highly expressed in gills and, in particular, mantle rim tissues. Orthologue sequences were identified in other species of the family Mytilidae, including Mytilus galloprovincialis, from which lectin MytiLec-1 was isolated and characterized in our previous studies. Thus, mytilid species contain lectins belonging to at least two distinct families (R-type lectins and mytilectins) that have a common β-trefoil fold structure but differing glycan-binding specificities. SeviL displayed notable cytotoxic (apoptotic) effects against various cultured cell lines (human breast, ovarian, and colonic cancer; dog kidney) that possess asialo-GM1 oligosaccharide at the cell surface. This cytotoxic effect was inhibited by the presence of anti-asialo-GM1 oligosaccharide antibodies. With HeLa ovarian cancer cells, SeviL showed dose- and time-dependent activation of kinase MKK3/6, p38 MAPK, and caspase-3/9. The transduction pathways activated by SeviL via the glycosphingolipid oligosaccharide were triggered apoptosis. DATABASE: Nucleotide sequence data have been deposited in the GenBank database under accession numbers MK434191, MK434192, MK434193, MK434194, MK434195, MK434196, MK434197, MK434198, MK434199, MK434200, and MK434201.
一种 15kDa 的凝集素，称为 SeviL，从贻贝（紫色分叉贻贝）中分离出来。SeviL 形成非共价二聚体，强烈结合神经节系列 GM1b 寡糖（Neu5Acɑ2-3Galβ1-3GalNAcβ1-4Galβ1-4Glc）及其前体，即去唾液酸-GM1（Galβ1-3GalNAcβ1-4Galβ1-4Glc）。SeviL 还与 SSEA-4 六糖的聚糖部分弱相互作用（Neu5Acα2-3Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc）。通过质谱法测定了凝集素的部分蛋白质序列，并通过转录组分析确定了完整序列。SeviL 由 129 个氨基酸组成，根据该折叠特征的 QxW 基序的存在，被归类为 R(icin B)-型凝集素。SeviL mRNA 在鳃中高度表达，特别是在套膜边缘组织中。在贻贝科的其他物种中也鉴定出了同源序列，包括从我们之前的研究中分离和表征的 Mytilus galloprovincialis 中的凝集素 MytiLec-1。因此，贻贝物种至少包含属于两个不同家族的凝集素（R 型凝集素和 mytilectins），它们具有共同的β三叶折叠结构，但糖结合特异性不同。SeviL 对具有细胞表面去唾液酸-GM1 寡糖的各种培养细胞系（人乳腺癌、卵巢癌和结肠癌；狗肾）表现出显著的细胞毒性（凋亡）作用。这种细胞毒性作用被抗去唾液酸-GM1 寡糖抗体的存在所抑制。用 HeLa 卵巢癌细胞，SeviL 显示出剂量和时间依赖性激活激酶 MKK3/6、p38 MAPK 和 caspase-3/9。通过糖脂寡糖激活的 SeviL 的转导途径触发了细胞凋亡。数据库：核苷酸序列数据已在 GenBank 数据库中以 MK434191、MK434192、MK434193、MK434194、MK434195、MK434196、MK434197、MK434198、MK434199、MK434200 和 MK434201 的登录号注册。
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