ERdj3, a stress-inducible endoplasmic reticulum DnaJ homologue, serves as a cofactor for BiP's interactions with unfolded substrates
ERdj3, a stress-inducible endoplasmic reticulum DnaJ homologue, serves as a cofactor for BiP's interactions with unfolded substrates
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DOI：
10.1091/mbc.e04-05-0434
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发表时间：
2005-01-01
影响因子：
3.3
通讯作者：
Hendershot, LM
中科院分区：
文献类型：
--
作者：
Shen, Y;Hendershot, LM
我们最近发现 ERdj3 是未组装的免疫球蛋白 (Ig) 重链：BiP 复合物的一个组成部分。 ERdj3 还与许多其他蛋白质底物结合，包括未折叠的轻链、非分泌的 Ig 轻链突变体和非允许温度下的 VSV-G ts045 突变体。我们产生了一种 ERdj3 突变体，该突变体无法在体外刺激 BiP 的 ATP 酶活性或在体内结合 BiP。该突变体保留了与未折叠蛋白质底物相互作用的能力，表明 ERdj3 直接与蛋白质结合，而不是通过与 BiP 相互作用。 BiP 与未折叠轻链的结合时间比 ERdj3 更长，ERdj3 最初与未折叠轻链相互作用，但在蛋白质折叠完成之前很快解离。这表明 ERdj3 可能首先与底物结合并抑制蛋白质聚集，直到 BiP 加入复合物，而 BiP 保持结合直到折叠完成。此外，我们的研究结果支持一个模型，其中与 BiP 的相互作用有助于触发 ERdj3 从底物：BiP 复合物中释放。
We recently identified ERdj3 as a component of unassembled immunoglobulin (Ig) heavy chain:BiP complexes. ERdj3 also associates with a number of other protein substrates, including unfolded light chains, a nonsecreted Ig light chain mutant, and the VSV-G ts045 mutant at the nonpermissive temperature. We produced an ERdj3 mutant that was unable to stimulate BiP's ATPase activity in vitro or to bind BiP in vivo. This mutant retained the ability to interact with unfolded protein substrates, suggesting that ERdj3 binds directly to proteins instead of via interactions with BiP. BiP remained bound to unfolded light chains longer than ERdj3, which interacted with unfolded light chains initially, but quickly disassociated before protein folding was completed. This suggests that ERdj3 may bind first to substrates and serve to inhibit protein aggregation until BiP joins the complex, whereas BiP remains bound until folding is complete. Moreover, our findings support a model where interactions with BiP help trigger the release of ERdj3 from the substrate:BiP complex.