ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria.
ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria.
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DOI：
10.1038/s41467-020-20381-z
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发表时间：
2021-01-05
影响因子：
16.6
通讯作者：
Amunts A
中科院分区：
文献类型：
--
作者：
Mühleip A;Kock Flygaard R;Ovciarikova J;Lacombe A;Fernandes P;Sheiner L;Amunts A
线粒体三磷酸腺苷合成酶在诱导膜曲形成嵴中起着关键作用。在引起疟疾和弓形虫病等疾病的尖端复合体中，观察到一种不寻常的冠状突起形态，但其结构基础尚不清楚。在这里，我们报告了顶复合体ATP合成酶组装成环状六聚体，这对于形成它们独特的脊是必不可少的。冷冻-EM用于确定六聚体的结构，该六聚体通过管腔区域寄生虫特异性亚基之间的相互作用而结合在一起。总体而言，我们确定了17个顶端复合体特异性亚基，以及一个最小的核编码亚基-a。该六聚体由三个二聚体组成，具有广泛的二聚体界面，包括结合的心磷脂和抑制剂IF1。冰冻切片和亚断层图像平均显示，在弯曲的顶膜区，六角体排列成约20兆吨的五角锥体。连接蛋白ATPTG11的敲除导致五角形金字塔的丢失，伴随着异常形状的脊状突起。综上所述，这表明独特的大分子排列对于维持尖脊的形态是至关重要的。对人类寄生虫弓形虫线粒体的结构和功能分析表明，其ATP合成酶组装成环状六聚体，以五角形金字塔的形式排列在一起，这是维持顶复合体中脊形态所必需的。
Mitochondrial ATP synthase plays a key role in inducing membrane curvature to establish cristae. In Apicomplexa causing diseases such as malaria and toxoplasmosis, an unusual cristae morphology has been observed, but its structural basis is unknown. Here, we report that the apicomplexan ATP synthase assembles into cyclic hexamers, essential to shape their distinct cristae. Cryo-EM was used to determine the structure of the hexamer, which is held together by interactions between parasite-specific subunits in the lumenal region. Overall, we identified 17 apicomplexan-specific subunits, and a minimal and nuclear-encoded subunit-a. The hexamer consists of three dimers with an extensive dimer interface that includes bound cardiolipins and the inhibitor IF1. Cryo-ET and subtomogram averaging revealed that hexamers arrange into ~20-megadalton pentagonal pyramids in the curved apical membrane regions. Knockout of the linker protein ATPTG11 resulted in the loss of pentagonal pyramids with concomitant aberrantly shaped cristae. Together, this demonstrates that the unique macromolecular arrangement is critical for the maintenance of cristae morphology in Apicomplexa. Structural and functional analysis of mitochondria from the human parasite Toxoplasma gondii reveals that its ATP synthase assembles into cyclic hexamers, arranged together in a form of pentagonal pyramids required for maintenance of cristae morphology in Apicomplexa.
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影响因子：
48
作者：
Barad BA;Echols N;Wang RY;Cheng Y;DiMaio F;Adams PD;Fraser JS
通讯作者：
Fraser JS
影响因子：
4.8
作者：
Bornhoevd, Carsten;Vogel, Frank;Reichert, Andreas S.
通讯作者：
Reichert, Andreas S.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1016/s0022-5320(69)80010-9
发表时间：
1969-01-01
期刊：
JOURNAL OF ULTRASTRUCTURE RESEARCH
影响因子：
--
作者：
AIKAWA, M;HUFF, CG;SPRINZ, H
通讯作者：
SPRINZ, H
DOI：
10.1107/s2059798318006551
发表时间：
2018-06-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Afonine PV;Poon BK;Read RJ;Sobolev OV;Terwilliger TC;Urzhumtsev A;Adams PD
通讯作者：
Adams PD