Cryo-EM structure of a monomeric yeast S. cerevisiae complex IV isolated with maltosides: Implications in supercomplex formation.
Cryo-EM structure of a monomeric yeast S. cerevisiae complex IV isolated with maltosides: Implications in supercomplex formation.
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DOI：
10.1016/j.bbabio.2022.148591
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发表时间：
2022-07
期刊：
影响因子：
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通讯作者：
Gabriel Ing;Andrew M. Hartley;N. Pinotsis;A. Maréchal
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文献类型：
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作者：
Gabriel Ing;Andrew M. Hartley;N. Pinotsis;A. Maréchal
在线粒体中，复合体IV （CIV）可以作为单体、二聚体或与其他呼吸复合体联合存在。酵母的原子结构。与配合物III （CIII）的超配合物（SC）中的cerevisiaeCIV指向与同源哺乳动物CIV结构相比显着构象变化的区域。这些变化涉及CIII-CIV界面上Cox5A的矩阵侧结构域，这可能是SC形成所必需的。为了研究这一点，我们解决了分离的单体CIV的结构。用低温电子显微镜在3.9 Å的amphipol A8-35中建立了铈。在这个Cox5A区域只观察到轻微的灵活性变化，排除了CIV与CIII相互作用的大构象变化，并证实了酵母Cox5A亚基与哺乳动物同源物相比的不同折叠。其他结构上的差异是缺少两个典型亚基，Cox12和Cox13，以及酵母菌CIV特有的Cox26。它们的缺失很可能是由于从III-IV型SC中分离CIV所用的蛋白质纯化方案所致。
In mitochondria, complex IV (CIV) can be found as a monomer, a dimer or in association with other respiratory complexes. The atomic structure of the yeastS. cerevisiaeCIV in a supercomplex (SC) with complex III (CIII) pointed to a region of significant conformational changes compared to the homologous mammalian CIV structures. These changes involved the matrix side domain of Cox5A at the CIII-CIV interface, and it was suggested that it could be required for SC formation. To investigate this, we solved the structure of the isolated monomeric CIV fromS. cerevisiaestabilised in amphipol A8–35 at 3.9 Å using cryo-electron microscopy. Only a minor change in flexibility was seen in this Cox5A region, ruling out large CIV conformational shift for interaction with CIII and confirming the different fold of the yeast Cox5A subunit compared to mammalian homologues. Other differences in structure were the absence of two canonical subunits, Cox12 and Cox13, as well as Cox26, which is unique to the yeast CIV. Their absence is most likely due to the protein purification protocol used to isolate CIV from the III-IV SC.