The molecular mechanisms underlying BiP-mediated gating of the Sec61 translocon of the endoplasmic reticulum.
The molecular mechanisms underlying BiP-mediated gating of the Sec61 translocon of the endoplasmic reticulum.
复制标题
BIP介导的分子机制的内质网的Sec61易位门控。
DOI：
10.1083/jcb.200409174
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发表时间：
2005-01-31
期刊：
影响因子：
--
通讯作者：
Johnson AE
中科院分区：
文献类型：
--
作者：
Alder NN;Shen Y;Brodsky JL;Hendershot LM;Johnson AE
内质网膜的 Sec61 易位子形成一个由腔内 Hsp70 伴侣 BiP 门控的水孔。我们探索了控制 BiP 介导的门控活性的分子机制，包括门控和 BiP ATP 酶循环之间的耦合，以及 BiP 的底物结合和 J 结构域结合区域的参与。通过测量掺入易位中间体新生链中的荧光探针的碰撞猝灭来测定易位子门控，所述易位中间体与含有各种BiP突变体和BiP底物的微粒体接合。我们的结果表明，BiP 必须采取 ADP 结合构象来密封易位子，并且孔的重新打开需要 ATP 结合诱导的构象变化。此外，孔闭合需要 BiP 和膜蛋白的底物结合区域和 J 结构域结合区域之间的功能相互作用。因此，BiP 介导易位子孔关闭和打开的机制类似于 Hsp70 伴侣与底物结合和解离的机制。
The Sec61 translocon of the endoplasmic reticulum membrane forms an aqueous pore that is gated by the lumenal Hsp70 chaperone BiP. We have explored the molecular mechanisms governing BiP-mediated gating activity, including the coupling between gating and the BiP ATPase cycle, and the involvement of the substrate-binding and J domain–binding regions of BiP. Translocon gating was assayed by measuring the collisional quenching of fluorescent probes incorporated into nascent chains of translocation intermediates engaged with microsomes containing various BiP mutants and BiP substrate. Our results indicate that BiP must assume the ADP-bound conformation to seal the translocon, and that the reopening of the pore requires an ATP binding–induced conformational change. Further, pore closure requires functional interactions between both the substrate-binding region and the J domain–binding region of BiP and membrane proteins. The mechanism by which BiP mediates translocon pore closure and opening is therefore similar to that in which Hsp70 chaperones associate with and dissociate from substrates.
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影响因子：
56.9
作者：
FLYNN, GC;CHAPPELL, TG;ROTHMAN, JE
通讯作者：
ROTHMAN, JE
影响因子：
7.8
作者：
Haigh, Nora G;Johnson, Arthur E
通讯作者：
Johnson, Arthur E
DOI：
10.1083/jcb.137.7.1483
发表时间：
1997-06-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Chevalier, M;Rhee, H;Blond, SY
通讯作者：
Blond, SY
DOI：
10.1073/pnas.93.11.5269
发表时间：
1996-05-28
影响因子：
11.1
作者：
Hendershot, L;Wei, JY;Argon, Y
通讯作者：
Argon, Y