Non-C-mannosylable mucin CYS domains hindered proper folding and secretion of mucin
Non-C-mannosylable mucin CYS domains hindered proper folding and secretion of mucin
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DOI：
10.1016/j.bbrc.2018.10.138
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发表时间：
2018-12-02
影响因子：
3.1
通讯作者：
Desseyn, Jean-Luc
中科院分区：
文献类型：
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作者：
Gouyer, Valerie;Demouveaux, Bastien;Desseyn, Jean-Luc
CYS结构域以多个拷贝存在于许多凝胶形成粘蛋白中。据信，CYS结构域可以以可逆的方式彼此相互作用，表明该结构域在凝胶形成中的关键作用。该结构域总是在其氨基末端序列中包含C-甘露糖基化基序WXXW，但CYS结构域是否是C-甘露糖基化的存在争议，并且该结构域的C-甘露糖基化的推定作用尚不清楚。我们制备了具有（WXXW -> AXXW）和不具有单个氨基酸突变的人粘蛋白MUC 5 B的重组CYS结构域，以及由大的Serf Thr/Pro区制成的迷你-5B粘蛋白，所述大的Serf Thr/Pro区侧接两个CYS结构域，所述两个CYS结构域在第一、第二或两个CYS结构域上具有WXXW基序或具有突变的AXXW基序。我们发现，单个CYS结构域和两个CYS结构域的迷你-5B粘蛋白必须是C-甘露糖基化的重组分子的有效成熟和分泌，否则，它们被保留在细胞中，并与内质网的常驻酶共定位。(C)2018爱思唯尔公司All rights reserved.
The CYS domain occurs in multiple copies in many gel-forming mucins. It is believed that CYS domains can interact with each other in a reversible manner, suggesting a key role of the domain in gel formation. This domain always contains in its amino-terminal sequence the C-mannosylation motif WXXW, but whether the CYS domain is C-mannosylated is debated, and the putative role of C-mannosylation of the domain is unclear. We prepared recombinant CYS domains of the human mucin MUC5B with (WXXW -> AXXW) and without a single amino acid mutation and mini-5B mucins made of a large Serf Thr/Pro region flanked by two CYS domains with the WXXW motif or with the mutated AXXW motif on the first, second or both CYS domains. We found that the single CYS domain and the two CYS domains of mini-5B mucin must be C-mannosylable for the efficient maturation and secretion of the recombinant molecules; otherwise, they are retained in the cell and co-localized with a resident enzyme of the endoplasmic reticulum. (C) 2018 Elsevier Inc. All rights reserved.