Mammalian mitochondrial electron transport chain complexes are the most important and complicated protein machinery in mitochondria.Although this system has been studied for more than a century,its composition and mol...Mammalian mitochondrial electron transport chain complexes are the most important and complicated protein machinery in mitochondria.Although this system has been studied for more than a century,its composition and molecular mechanism are still largely unknown.Here we report the high-resolution cryo-electron microscopy(Cryo-EM)structures of porcine respiratory chain megacomplex-Ⅰ_(2)Ⅲ_(2)Ⅳ_(2)(MCⅠ_(2)Ⅲ_(2)Ⅳ_(2))in five different conformations,including State 1,State 2,Mid 1,Mid 2,and Mid 3.High-resolution Cryo-EM imaging,combined with super-resolution gated stimulated emission depletion microscopy(gSTED),strongly supports the formation of MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)in live cells.Each MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)structure contains 141 subunits(70 different kinds of peptides,2.9 MDa)in total with 240 transmembrane helices.The mutual influence among CⅠ,CⅢ,and CⅣshown in the MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)structure suggests this megacomplex could act as an integral unit in electron transfer and proton pumping.The conformational changes from different states suggest a plausible regulatory mechanism for the MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)activation/deactivation process.展开更多
With the support by the National Natural Science Foundation of China,the group of Yang Maojun（杨茂君）firstly solved the medium resolution structure of human respiratory megacomplex Ⅰ2Ⅲ2Ⅳ2 and the atomic structure...With the support by the National Natural Science Foundation of China,the group of Yang Maojun（杨茂君）firstly solved the medium resolution structure of human respiratory megacomplex Ⅰ2Ⅲ2Ⅳ2 and the atomic structure of the supercomplex Ⅰ1Ⅲ2Ⅳ1in the world.The results were published in Cell(2017,展开更多
Respirasome, a huge molecular machine that carries out cellular respiration, has gained growing attention since its discovery, because respiration is the most indis- pensable biological process in almost all living cr...Respirasome, a huge molecular machine that carries out cellular respiration, has gained growing attention since its discovery, because respiration is the most indis- pensable biological process in almost all living crea- tures. The concept of respirasome has renewed our understanding of the respiratory chain organization, and most recently, the structure of respirasome solved by Yang＇s group from Tsinghua University （Gu et al. Nature 237（7622）：639-643, 2016） firstly presented the detailed interactions within this huge molecular machine, and provided important information for drug design and screening. However, the study of cellular respiration went through a long history. Here, we briefly showed the detoured history of respiratory chain investigation, and then described the amazing structure of respirasome.展开更多
Respirasome,as a vital part of the oxidative phosphorylation system,undertakes the task of transferring electrons from the electron donors to oxygen and produces a proton concentration gradient across the inner mitoch...Respirasome,as a vital part of the oxidative phosphorylation system,undertakes the task of transferring electrons from the electron donors to oxygen and produces a proton concentration gradient across the inner mitochondrial membrane through the coupled translocation of protons.Copious research has been carried out on this lynchpin of respiration.From the discovery of individual respiratory complexes to the report of the high-resolution structure of mammalian respiratory supercomplex I1III2IV1,scientists have gradually uncovered the mysterious veil of the electron transport chain(ETC).With the discovery of the mammalian respiratory mega complex I2III2IV2,a new perspective emerges in the research field of the ETC.Behind these advances glitters the light of the revolution in both theory and technology.Here,we give a short review about how scientists‘see’the structure and the mechanism of respirasome from the macroscopic scale to the atomic scale during the past decades.展开更多
基金supported by funds from the National Natural Science Foundation of China(32030056 and 32100962)the Tsinghua University Spring Breeze Fund(20201080572)+4 种基金the National Science Fund for Distinguished Young Scholars(3210110055)the China Postdoctoral Science Foundation(2020TQ0178,2020M680519,and 2020M680521)the Guangdong Basic and Applied Basic Research Foundation(2023B1515020039)the Shenzhen Science and Technology Program(RCYX20221008092904016)the Shenzhen University 2035 Program for Excellent Research(2022C012).
文摘Mammalian mitochondrial electron transport chain complexes are the most important and complicated protein machinery in mitochondria.Although this system has been studied for more than a century,its composition and molecular mechanism are still largely unknown.Here we report the high-resolution cryo-electron microscopy(Cryo-EM)structures of porcine respiratory chain megacomplex-Ⅰ_(2)Ⅲ_(2)Ⅳ_(2)(MCⅠ_(2)Ⅲ_(2)Ⅳ_(2))in five different conformations,including State 1,State 2,Mid 1,Mid 2,and Mid 3.High-resolution Cryo-EM imaging,combined with super-resolution gated stimulated emission depletion microscopy(gSTED),strongly supports the formation of MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)in live cells.Each MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)structure contains 141 subunits(70 different kinds of peptides,2.9 MDa)in total with 240 transmembrane helices.The mutual influence among CⅠ,CⅢ,and CⅣshown in the MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)structure suggests this megacomplex could act as an integral unit in electron transfer and proton pumping.The conformational changes from different states suggest a plausible regulatory mechanism for the MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)activation/deactivation process.
文摘With the support by the National Natural Science Foundation of China,the group of Yang Maojun（杨茂君）firstly solved the medium resolution structure of human respiratory megacomplex Ⅰ2Ⅲ2Ⅳ2 and the atomic structure of the supercomplex Ⅰ1Ⅲ2Ⅳ1in the world.The results were published in Cell(2017,
基金This work was supported by funds from the National Basic Research Program （973 Program） （Nos. 2016YFA0501101 and 2012CB911101）, and the National Science Fund for Distinguished Young Scholars （No. 3163000168） and the National Natural Science Foundation of China （Grant Nos. 31030020 and 31170679）.
文摘Respirasome, a huge molecular machine that carries out cellular respiration, has gained growing attention since its discovery, because respiration is the most indis- pensable biological process in almost all living crea- tures. The concept of respirasome has renewed our understanding of the respiratory chain organization, and most recently, the structure of respirasome solved by Yang＇s group from Tsinghua University （Gu et al. Nature 237（7622）：639-643, 2016） firstly presented the detailed interactions within this huge molecular machine, and provided important information for drug design and screening. However, the study of cellular respiration went through a long history. Here, we briefly showed the detoured history of respiratory chain investigation, and then described the amazing structure of respirasome.
基金Tsinghua University Branch of China National Center for Protein Sciences(Beijing)for providing the facility support.
文摘Respirasome,as a vital part of the oxidative phosphorylation system,undertakes the task of transferring electrons from the electron donors to oxygen and produces a proton concentration gradient across the inner mitochondrial membrane through the coupled translocation of protons.Copious research has been carried out on this lynchpin of respiration.From the discovery of individual respiratory complexes to the report of the high-resolution structure of mammalian respiratory supercomplex I1III2IV1,scientists have gradually uncovered the mysterious veil of the electron transport chain(ETC).With the discovery of the mammalian respiratory mega complex I2III2IV2,a new perspective emerges in the research field of the ETC.Behind these advances glitters the light of the revolution in both theory and technology.Here,we give a short review about how scientists‘see’the structure and the mechanism of respirasome from the macroscopic scale to the atomic scale during the past decades.
