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完整ATP合酶二聚体的结构揭示了线粒体内膜形态的分子基础。

Structure of a Complete ATP Synthase Dimer Reveals the Molecular Basis of Inner Mitochondrial Membrane Morphology.

作者信息

Hahn Alexander, Parey Kristian, Bublitz Maike, Mills Deryck J, Zickermann Volker, Vonck Janet, Kühlbrandt Werner, Meier Thomas

机构信息

Department of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany.

Institute of Biochemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.

出版信息

Mol Cell. 2016 Aug 4;63(3):445-56. doi: 10.1016/j.molcel.2016.05.037. Epub 2016 Jun 30.

DOI:10.1016/j.molcel.2016.05.037
PMID:27373333
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4980432/
Abstract

We determined the structure of a complete, dimeric F1Fo-ATP synthase from yeast Yarrowia lipolytica mitochondria by a combination of cryo-EM and X-ray crystallography. The final structure resolves 58 of the 60 dimer subunits. Horizontal helices of subunit a in Fo wrap around the c-ring rotor, and a total of six vertical helices assigned to subunits a, b, f, i, and 8 span the membrane. Subunit 8 (A6L in human) is an evolutionary derivative of the bacterial b subunit. On the lumenal membrane surface, subunit f establishes direct contact between the two monomers. Comparison with a cryo-EM map of the F1Fo monomer identifies subunits e and g at the lateral dimer interface. They do not form dimer contacts but enable dimer formation by inducing a strong membrane curvature of ∼100°. Our structure explains the structural basis of cristae formation in mitochondria, a landmark signature of eukaryotic cell morphology.

摘要

我们通过冷冻电镜和X射线晶体学相结合的方法,确定了来自解脂耶氏酵母线粒体的完整二聚体F1Fo - ATP合酶的结构。最终结构解析出了60个二聚体亚基中的58个。Fo中a亚基的水平螺旋围绕c环转子,总共6个分配给a、b、f、i和8亚基的垂直螺旋跨越膜。8亚基(人类中的A6L)是细菌b亚基的进化衍生物。在膜内腔表面,f亚基在两个单体之间建立直接接触。与F1Fo单体的冷冻电镜图谱比较,在二聚体侧向界面处鉴定出e和g亚基。它们不形成二聚体接触,但通过诱导约100°的强膜曲率来促进二聚体形成。我们的结构解释了线粒体中嵴形成的结构基础,这是真核细胞形态的标志性特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/4a4ea3ca5680/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/607fe696ab79/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/69e661e99d4d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/b472f717a640/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/dd646599fbaa/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/f60b146f68a4/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/01e77c436add/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/2b40badfde8b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/4a4ea3ca5680/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/607fe696ab79/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/69e661e99d4d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/b472f717a640/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/dd646599fbaa/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/f60b146f68a4/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/01e77c436add/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/2b40badfde8b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778a/4980432/4a4ea3ca5680/gr7.jpg

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Structure and conformational states of the bovine mitochondrial ATP synthase by cryo-EM.
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The mitochondrial intermembrane space - a permanently proteostasis-challenged compartment.线粒体膜间隙——一个蛋白质稳态持续面临挑战的区室。
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4D quantitative proteomics of ovarian granulosa cells reveals the involvement of oxidative phosphorylation in non-elderly women with diminished ovarian reserve.卵巢颗粒细胞的4D定量蛋白质组学揭示了氧化磷酸化在卵巢储备功能减退的非老年女性中的作用。
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