R992C (p.R1192C) Substitution in collagen II alters the structure of mutant molecules and induces the unfolded protein response.
R992C (p.R1192C) Substitution in collagen II alters the structure of mutant molecules and induces the unfolded protein response.
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DOI：
10.1016/j.jmb.2009.05.004
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发表时间：
2009-07-10
影响因子：
5.6
通讯作者：
Fertala, Andrzej
中科院分区：
文献类型：
--
作者：
Chung, Hye Jin;Jensen, Deborah A.;Gawron, Katarzyna;Steplewski, Andrzej;Fertala, Andrzej
我们研究了与II型胶原中R992C（p.R1192C）替代相关的脊椎骨骺发育不良（SED）的分子基础。在蛋白质水平上，我们分析了突变分子的结构和完整性，在细胞水平上，我们专门研究了R992C II型胶原蛋白的存在对宿主细胞中发生的生物学过程的影响。我们的研究表明，突变型胶原蛋白II分子的特征在于改变电泳迁移率，相对较低的热稳定性，非典型二硫键的存在下，和缓慢的速率分泌到细胞外空间。对突变分子存在的细胞反应的分析表明，不耐热胶原蛋白II的过度积累与“未折叠蛋白反应”的激活和宿主细胞凋亡的增加有关。总的来说，这些数据表明，SED的分子机制可能不仅由细胞外胶原基质的结构变化驱动，而且由突变型胶原II分子的存在激活的细胞内过程驱动。
We investigated the molecular bases of spondyloepiphyseal dysplasia (SED) associated with the R992C (p.R1192C) substitution in collagen II. At the protein level we analyzed the structure and integrity of mutant molecules, and at the cellular level we specifically studied the effects of the presence of the R992C collagen II on the biological processes taking place in host cells. Our studies demonstrated that mutant collagen II molecules were characterized by altered electrophoretic mobility, relatively low thermostability, the presence of atypical disulfide bonds, and slow rates of secretion into the extracellular space. Analyses of cellular responses to the presence of the mutant molecules showed that excessive accumulation of thermolabile collagen II was associated with the activation of an “unfolded protein response” and an increase in apoptosis of host cells. Collectively, these data suggest that molecular mechanisms of SED may be driven not only by structural changes in the architecture of extracellular collagenous matrices, but also by intracellular processes activated by the presence of mutant collagen II molecules.
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影响因子：
6.2
作者：
Donahue, LR;Chang, B;Davisson, MT
通讯作者：
Davisson, MT
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作者：
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作者：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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影响因子：
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作者：
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