Structural snapshots of the cellular folded protein translocation machinery Bcs1.
Structural snapshots of the cellular folded protein translocation machinery Bcs1.
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DOI：
10.1111/febs.15576
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Xia D
中科院分区：
文献类型：
--
作者：
Xia D
Bcs1(Bcs1)蛋白促进铁硫蛋白或isp以折叠形式跨线粒体内膜运输。呼吸链的关键元件--复合体III的组装需要isp。Bcs1在三个核苷酸状态的结构提供了对isp易位和复合体III组装的机制的洞察，并揭示了Bcs1突变引起疾病的分子基础。去往细胞内外不同位置的蛋白质必须经常以未折叠的形式穿过细胞膜。当被转位的蛋白质需要保持折叠状态时，就会使用专门的细胞运输机械。其中一个这样的机器是膜结合的AAA蛋白Bcs1(Bcs1)，它帮助铁硫蛋白穿过线粒体内膜，铁硫蛋白是呼吸复合体III的一个重要亚基。最近对小鼠和酵母Bcs1在三种不同核苷酸状态下的结构测定表明，它与同源七聚体结合，至少有两种截然不同的构象。Apo和ADP结合的结构相似，都含有一个大的底物结合空腔，可进入线粒体基质空间，通过ATP结合时ATPase结构域的协同运动而收缩，这表明结合的底物可以被推过膜。ATP水解驱动底物释放，并将Bcs1构象重置为apo/ADP形式。这些结构揭示了折叠蛋白跨膜转运的机制，提供了更好的理解呼吸复合体III的组装过程，并将疾病相关突变的临床表现与它们在3D结构中的位置相关联。
The protein Bcs1 (Bcs1) facilitates the transport of iron‐sulfur protein or ISP in a folded form across the inner membranes of mitochondria. ISP is needed for the assembly of Complex III, a key element of the respiratory chain. Structures of Bcs1 in three nucleotide states offer insights into the mechanisms of ISP translocation and Complex III assembly and shed light on the molecular basis of diseases caused by mutations in Bcs1. Proteins destined to various intra‐ and extra‐cellular locations must traverse membranes most frequently in an unfolded form. When the proteins being translocated need to remain in a folded state, specialized cellular transport machinery is used. One such machine is the membrane‐bound AAA protein Bcs1 (Bcs1), which assists the iron‐sulfur protein, an essential subunit of the respiratory Complex III, across the mitochondrial inner membrane. Recent structure determinations of mouse and yeast Bcs1 in three different nucleotide states reveal its homo‐heptameric association and at least two dramatically different conformations. The apo and ADP‐bound structures are similar, both containing a large substrate‐binding cavity accessible to the mitochondrial matrix space, which contracts by concerted motion of the ATPase domains upon ATP binding, suggesting that bound substrate could then be pushed across the membrane. ATP hydrolysis drives substrate release and resets Bcs1 conformation back to the apo/ADP form. These structures shed new light on the mechanism of folded protein translocation across a membrane, provide better understanding on the assembly process of the respiratory Complex III, and correlate clinical presentations of disease‐associated mutations with their locations in the 3D structure.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
2.9
作者：
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