Sec61 与 Mpd1 相互作用对内质网相关降解的影响。
Effect of Sec61 interaction with Mpd1 on endoplasmic reticulum-associated degradation.
机构信息
Faculty of Natural Sciences and Technology, Saarland University, Saarbruecken, Germany.
Proteomics Core Facility, EMBL, Heidelberg, Germany.
出版信息
PLoS One. 2019 Jan 25;14(1):e0211180. doi: 10.1371/journal.pone.0211180. eCollection 2019.
Proteins that misfold in the endoplasmic reticulum (ER) are transported back to the cytosol for ER-associated degradation (ERAD). The Sec61 channel is one of the candidates for the retrograde transport conduit. Channel opening from the ER lumen must be triggered by ERAD factors and substrates. Here we aimed to identify new lumenal interaction partners of the Sec61 channel by chemical crosslinking and mass spectrometry. In addition to known Sec61 interactors we detected ERAD factors including Cue1, Ubc6, Ubc7, Asi3, and Mpd1. We show that the CPY* ERAD factor Mpd1 binds to the lumenal Sec61 hinge region. Deletion of the Mpd1 binding site reduced the interaction between both proteins and caused an ERAD defect specific for CPY* without affecting protein import into the ER or ERAD of other substrates. Our data suggest that Mpd1 binding to Sec61 is a prerequisite for CPY* ERAD and confirm a role of Sec61 in ERAD of misfolded secretory proteins.
在粗面内质网（ER）中错误折叠的蛋白质被运回到细胞质中进行 ER 相关降解（ERAD）。Sec61 通道是逆行运输管道的候选者之一。通道从 ER 腔的打开必须由 ERAD 因子和底物触发。在这里，我们旨在通过化学交联和质谱鉴定 Sec61 通道的新腔相互作用伙伴。除了已知的 Sec61 相互作用因子外，我们还检测到 ERAD 因子，包括 Cue1、Ubc6、Ubc7、 Asi3 和 Mpd1。我们表明，CPY* ERAD 因子 Mpd1 结合到 Sec61 的腔性铰链区域。删除 Mpd1 结合位点减少了两种蛋白质之间的相互作用，并导致仅针对 CPY* 的 ERAD 缺陷，而不影响蛋白质向 ER 的导入或其他底物的 ERAD。我们的数据表明，Mpd1 与 Sec61 的结合是 CPY* ERAD 的前提条件，并证实了 Sec61 在错误折叠分泌蛋白的 ERAD 中的作用。
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