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| Open AccessEuglena’s atypical respiratory chain adapts to the discoidal cristae and flexible metabolism
Euglena gracilis is a model organism of the eukaryotic supergroup Discoba, single-celled organisms containing mitochondria with discoid cristae. Here, the authors report structures of Euglena’s transport chain supercomplex to reveal their distinctive architecture and working mechanisms.
- Zhaoxiang He
- , Mengchen Wu
- & Long Zhou
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Article
| Open AccessStructural insights into functional properties of the oxidized form of cytochrome c oxidase
Using resonance Raman spectroscopy and serial femtosecond X-ray crystallography, the authors show the heme a3 iron and CuB in the resting oxidized form of Cytochrome c Oxidase are coordinated by a hydroxide ion and a water molecule, respectively.
- Izumi Ishigami
- , Raymond G. Sierra
- & Denis L. Rousseau
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Article
| Open AccessWeak acids produced during anaerobic respiration suppress both photosynthesis and aerobic respiration
The processes of photosynthesis, aerobic and anaerobic respiration (fermentation) power life on Earth. Here, using mainly green alga Chlamydomonas, the authors find that the weak acids produced during fermentation could chemically suppress both photosynthesis and aerobic respiration.
- Xiaojie Pang
- , Wojciech J. Nawrocki
- & Lijin Tian
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Article
| Open AccessFunctional decomposition of metabolism allows a system-level quantification of fluxes and protein allocation towards specific metabolic functions
Quantifying the contribution of individual molecular components to complex cellular processes is a grand challenge in systems biology. Here, the authors present a general theoretical framework (Functional Decomposition of Metabolism, FDM) to quantify the contribution of every metabolic reaction to metabolic functions, e.g. the synthesis of biomass building blocks.
- Matteo Mori
- , Chuankai Cheng
- & Terence Hwa
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Article
| Open AccessMechanism of ATP hydrolysis dependent rotation of bacterial ATP synthase
The ATP synthase FoF1 undergoes rotation in discrete 120° steps. Using cryo-EM analysis, the authors characterise intermediate structures within these 120° steps at 81°, 83°, 91°, and 101°. This shows that FoF1 undergoes a total of 15 steps in a 360° rotation, exhibiting multiple discreet movements per full rotation as opposed to one fluid motion.
- Atsuki Nakano
- , Jun-ichi Kishikawa
- & Ken Yokoyama
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Article
| Open AccessStructures of Tetrahymena thermophila respiratory megacomplexes on the tubular mitochondrial cristae
Tetrahymena thermophila possesses tubular mitochondrial cristae and a highly divergent electron transport chain. Here the authors report cryo-EM structures of its half ring-shaped ~8 MDa megacomplex IV2 + (I + III2 + II)2 and ~10.6 MDa megacomplex (IV2 + I + III2 + II)2 adapted to the cristae membrane curvature.
- Fangzhu Han
- , Yiqi Hu
- & Long Zhou
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Article
| Open AccessMolecular determinants of inhibition of UCP1-mediated respiratory uncoupling
Combining molecular dynamic simulations with in vivo functional assays, Gagelin et al. identified unique molecular features of the mitochondrial carrier uncoupling protein 1 that are crucial to its inhibition by nucleotides
- Antoine Gagelin
- , Corentin Largeau
- & Bruno Miroux
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Article
| Open AccessDynamic fluctuations in a bacterial metabolic network
The interconnected network of cellular metabolism is potentially prone to generating oscillatory behaviour. Here, the authors use single-cell FRET measurements of pyruvate levels to reveal large periodic fluctuations in bacterial glycolysis.
- Shuangyu Bi
- , Manika Kargeti
- & Victor Sourjik
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Article
| Open AccessMolecular mechanism on forcible ejection of ATPase inhibitory factor 1 from mitochondrial ATP synthase
IF1 is a natural inhibitor of mitochondrial FoF1-ATP synthase, which blocks catalysis and rotation of the F1 motor. Here, the authors show the rotational-direction-dependence of activation from IF1 inhibition, with IF1 being readily dissociated when F1 rotates to the clockwise direction.
- Ryohei Kobayashi
- , Hiroshi Ueno
- & Hiroyuki Noji
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Article
| Open AccessStructure of a monomeric photosystem I core associated with iron-stress-induced-A proteins from Anabaena sp. PCC 7120
IsiAs are unique light-harvesting complexes in cyanobacteria. Here, authors solved the structure of a PSI monomer associated with six IsiAs from Anabaena by cryo-EM, which provide insights into molecular diversity and functions of different IsiAs.
- Ryo Nagao
- , Koji Kato
- & Jian-Ren Shen
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Article
| Open AccessRhodobacter capsulatus forms a compact crescent-shaped LH1–RC photocomplex
Rhodobacter capsulatus is a favored model organism for studying bacterial photosynthesis. Here the authors present a structure of its light-harvesting–reaction center complex, which reveals that it forms a crescent shape containing only 10 LH1 αβ-subunits.
- Kazutoshi Tani
- , Ryo Kanno
- & Zheng-Yu Wang-Otomo
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Article
| Open AccessCrystal structure of the Na+/H+ antiporter NhaA at active pH reveals the mechanistic basis for pH sensing
By determining the crystal structure of the Na + /H + antiporter NhaA at active pH, the authors show how substrate accessibility to the ion-binding site can be controlled by pH sensitive switch located on the cytoplasmic surface.
- Iven Winkelmann
- , Povilas Uzdavinys
- & David Drew
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Article
| Open AccessPurification and structural characterization of the Na+-translocating ferredoxin: NAD+ reductase (Rnf) complex of Clostridium tetanomorphum
Rnf reversibly reduces NAD+ by ferredoxin coupled with Na+/H+ pumping for microbial ion gradient or reduced ferredoxin formation. Here, a cryo-EM structure provides information about the participating iron and flavin cofactors, the electron transfer route and the putative Na+ passage.
- Stella Vitt
- , Simone Prinz
- & Wolfgang Buckel
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Article
| Open AccessMitochondrial network configuration influences sarcomere and myosin filament structure in striated muscles
How different physical configurations between sarcomeres and mitochondria alter energetic support for contractile function of skeletal muscle is not clear. Here the authors use advanced 3D imaging and analysis techniques to show how space is made for mitochondria within the tightly packed sarcomere networks of striated muscle cells.
- Prasanna Katti
- , Alexander S. Hall
- & Brian Glancy
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Article
| Open AccessMolecular asymmetry of a photosynthetic supercomplex from green sulfur bacteria
Cryo-EM reveals an asymmetric bacterial photosynthetic supercomplex built upon a homodimeric reaction center core. The structure provides mechanistic insights into light excitation transfer and a possible evolutionary transition intermediate of photosynthetic machinery.
- Ryan Puskar
- , Chloe Du Truong
- & Po-Lin Chiu
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Article
| Open AccessStructure of the membrane-bound formate hydrogenlyase complex from Escherichia coli
New cryo-EM structures of the formate hydrogenlyase complex from the model bacterium E. coli clarify how electrons and protons move through the complex and are combined to make H2 gas. The complex shows important similarities and differences to related bioenergetic complexes across the tree of life.
- Ralf Steinhilper
- , Gabriele Höff
- & Bonnie J. Murphy
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Article
| Open AccessStructure and function of H+/K+ pump mutants reveal Na+/K+ pump mechanisms
Here, the authors study ion transport mechanisms by introducing mutations to convert an electroneutral proton/potassium pump into a prototypical electrogenic sodium/potassium pump, explaining their selectivity and phosphorylation mechanisms.
- Victoria C. Young
- , Hanayo Nakanishi
- & Kazuhiro Abe
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Article
| Open AccessPost-translational amino acid conversion in photosystem II as a possible origin of photosynthetic oxygen evolution
How photosynthetic oxygen evolution is originated on ancient Earth is unknown. Here, the authors find that some amino acid residues at the ligand sites of the Mn cluster can be posttranslationally converted to the original carboxylate residues, which could have contributed to the evolutionary process of photosynthetic oxygen evolution.
- Yuichiro Shimada
- , Takehiro Suzuki
- & Takumi Noguchi
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Article
| Open AccessLaboratory evolution of synthetic electron transport system variants reveals a larger metabolic respiratory system and its plasticity
The bacterial respiratory electron transport system (ETS) is branched to allow condition-specific modulation of energy metabolism. Here the authors examine the systems level properties of aerobic electron transport system using adaptive laboratory evolution and multi-omics analyses.
- Amitesh Anand
- , Arjun Patel
- & Bernhard O. Palsson
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Article
| Open AccessSubstrate binding in the mitochondrial ADP/ATP carrier is a step-wise process guiding the structural changes in the transport cycle
The mitochondrial ADP/ATP carrier transports adenine nucleotides. Here, authors identify the residues involved in substrate binding. One set forms the central substrate binding site and two asparagine/arginine pairs help to guide the substrates during the transport cycle.
- Vasiliki Mavridou
- , Martin S. King
- & Edmund R. S. Kunji
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Article
| Open AccessTriplet-driven chemical reactivity of β-carotene and its biological implications
The endoperoxides of β-carotene play a key role in signaling of photooxidative stress in plant cells and are regarded as the products of chemical deactivation of singlet oxygen. The authors show that these compounds are instead formed in a reaction between oxygen and β-carotene in their triplet states, revealing the importance of the triplet states in the photoprotection of photosynthetic apparatus.
- Mateusz Zbyradowski
- , Mariusz Duda
- & Leszek Fiedor
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Article
| Open AccessStructure of ATP synthase under strain during catalysis
CryoEM of mitochondrial ATP synthase frozen during rotary catalysis reveals dramatic conformational changes in the peripheral stalk subcomplex, which enable the enzyme’s efficient synthesis of ATP.
- Hui Guo
- & John L. Rubinstein
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Article
| Open AccessAsymmetric structure of the native Rhodobacter sphaeroides dimeric LH1–RC complex
Rhodobacter sphaeroides is a model organism for studying bacterial photosynthesis. Here, the authors present structures of its native dimeric and a protein-U-lacking monomeric light-harvesting-reaction center complexes, which reveal asymmetric features for the dimer and an altered shape for the monomer.
- Kazutoshi Tani
- , Ryo Kanno
- & Zheng-Yu Wang-Otomo
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Article
| Open AccessStructural snapshots of V/A-ATPase reveal the rotary catalytic mechanism of rotary ATPases
The rotary ATPases use a rotary catalytic mechanism to drive transmembrane proton movement powered by ATP hydrolysis. Here, the authors report a collection of V/A-ATPase V1 domain structures, providing insights into rotary mechanism of the enzyme and potentially other rotary motor proteins driven by ATP hydrolysis.
- J. Kishikawa
- , A. Nakanishi
- & K. Yokoyama
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Article
| Open AccessBacterial F-type ATP synthases follow a well-choreographed assembly pathway
ATPases are the macromolecular machines for cellular energy production. Here the authors investigate factors that govern the assembly of the F1 complex from a bacterial F-type ATPase and relate differences in activity of complexes assembled in cells and in vitro to structural changes.
- Khanh Vu Huu
- , Rene Zangl
- & Nina Morgner
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Article
| Open AccessStructural basis for safe and efficient energy conversion in a respiratory supercomplex
Aerobic energy metabolism is driven by proton-pumping respiratory supercomplexes. The study reports the structural basis for energy conversion in such supercomplex. It may aid metabolic engineering and drug design against diphtheria and tuberculosis.
- Wei-Chun Kao
- , Claire Ortmann de Percin Northumberland
- & Carola Hunte
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Article
| Open AccessHigh-intensity training induces non-stoichiometric changes in the mitochondrial proteome of human skeletal muscle without reorganisation of respiratory chain content
Exercise training can be therapeutic but how mitochondria respond remains unclear. Here, the authors use multiple omics techniques to reveal a complex network of non-stoichiometric mitochondrial adaptations that are prioritized or deprioritised during different phases of exercise training.
- Cesare Granata
- , Nikeisha J. Caruana
- & David J. Bishop
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Article
| Open AccessStructural dynamics in the water and proton channels of photosystem II during the S2 to S3 transition
The oxygen-evolving complex in Photosystem II (PSII) catalyzes the light-driven oxidation of water to oxygen and it is still under debate how the water reaches the active site. Here, the authors analyse time-resolved XFEL-based crystal structures of PSII that were determined at room temperature and report the structures of the waters in the putative channels surrounding the active site at various time-points during the reaction cycle and conclude that the O1 channel is the likely water intake pathway and the Cl1 channel the likely proton release pathway.
- Rana Hussein
- , Mohamed Ibrahim
- & Junko Yano
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Article
| Open AccessGastric proton pump with two occluded K+ engineered with sodium pump-mimetic mutations
The gastric H+,K+-ATPase is a proton pump that creates the acidic environment of the stomach lumen, maintaining high proton gradient across the gastric mucosa cell membrane. Here, structural analysis of rationally designed H+,K+-ATPase mutants provides insight into this and other P-type ATPases cation binding stoichiometry and mechanisms.
- Kazuhiro Abe
- , Kenta Yamamoto
- & Atsunori Oshima
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Article
| Open AccessFunctional basis of electron transport within photosynthetic complex I
Photosynthetic Complex I (PS-CI) is proposed to couple ferredoxin oxidation and plastoquinone reduction to proton pumping across thylakoid membranes. Here the authors determine the reduction potentials of the iron-sulphur clusters of PS-CI and thus the bioenergetics of the electron transfer relay.
- Katherine H. Richardson
- , John J. Wright
- & Maxie M. Roessler
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Article
| Open AccessThe cryo-EM structure of the bd oxidase from M. tuberculosis reveals a unique structural framework and enables rational drug design to combat TB
M. tuberculosis cytochrome bd oxidase is of interest as a TB drug target. Here, the authors present the 2.5 Å cryo-EM structure of M. tuberculosis cytochrome bd oxidase and identify a disulfide bond within the canonical quinol binding and oxidation domain (Q-loop) and a menaquinone-9 binding site at heme b595.
- Schara Safarian
- , Helen K. Opel-Reading
- & Hartmut Michel
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Article
| Open AccessDefining the molecular mechanisms of the mitochondrial permeability transition through genetic manipulation of F-ATP synthase
The nature of the mitochondrial permeability transition pore (PTP) is still under debate. Here, through genetically modified F-ATP synthase, the authors show that PTP formation can be mediated by F-ATP synthase or by adenine nucleotide translocator, suggesting the existence of distinct but related permeability pathways.
- Andrea Carrer
- , Ludovica Tommasin
- & Paolo Bernardi
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Article
| Open AccessA genome-scale metabolic model of Saccharomyces cerevisiae that integrates expression constraints and reaction thermodynamics
Formulating metabolic networks mathematically can help researchers study metabolic diseases and optimize the production of industrially important molecules. Here, the authors propose a framework that allows to model eukaryotic metabolism considering gene expression and thermodynamic constraints.
- Omid Oftadeh
- , Pierre Salvy
- & Vassily Hatzimanikatis
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Article
| Open AccessThioesterase superfamily member 1 undergoes stimulus-coupled conformational reorganization to regulate metabolism in mice
Cold exposure activates thermogenesis and fatty acid oxidation in brown fat, a process suppressed by Them1. Here, the authors show that cold induces Them1 phosphorylation and loss of puncta that suppress fatty acid use, leading to a diffuse localization and increased energy expenditure in mice.
- Yue Li
- , Norihiro Imai
- & Susan J. Hagen
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Article
| Open AccessThe quantitative metabolome is shaped by abiotic constraints
Evolution selects for the fittest but must operate within the realm of the physically possible. Here, the authors present a theoretical framework that allows them to explore how ten abiotic constraints can shape the operation, regulation, and adaptation of metabolism in E. coli.
- Amir Akbari
- , James T. Yurkovich
- & Bernhard O. Palsson
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Article
| Open AccessCrystal structure of a photosynthetic LH1-RC in complex with its electron donor HiPIP
The high potential iron-sulfur (HiPIP) proteins are direct electron donors to the light-harvesting-reaction center complexes (LH1-RC) in photosynthetic β- and γ-Proteobacteria. Here, the authors present the 2.9 Å crystal structure of the HiPIP-bound LH1-RC complex from the thermophilic purple sulfur bacterium Thermochromatium tepidum and discuss mechanistic implications for the electron transfer pathway.
- Tomoaki Kawakami
- , Long-Jiang Yu
- & Zheng-Yu Wang-Otomo
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Article
| Open AccessMorphological bases of phytoplankton energy management and physiological responses unveiled by 3D subcellular imaging
Phytoplankton account for a large proportion of global primary production and comprise a number of phylogenetically distinct lineages. Here, Uwizeye et al. use FIB-SEM to study ultrastructural plasticity of 7 distinct taxa and describe how subcellular organisation is linked to energy metabolism.
- Clarisse Uwizeye
- , Johan Decelle
- & Giovanni Finazzi
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Article
| Open AccessStructural basis for a complex I mutation that blocks pathological ROS production
Reactive oxygen species (ROS) production by reverse electron transfer (RET) through complex I is thought to cause tissue damage from heart attacks. Here, the authors combine in vivo work with biochemical and cryo-EM analyses to characterize the effects of a P25L mutation in the ND6 subunit of mitochondrial complex I. They observe that this mutation does not affect oxidative phosphorylation but renders complex I unable to generate ROS by RET: ND6-P25L mice are protected against cardiac ischaemia–reperfusion injury, thus providing evidence for the proposed role of ROS production in myocardial infarction.
- Zhan Yin
- , Nils Burger
- & Judy Hirst
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Article
| Open AccessEssential role of accessory subunit LYRM6 in the mechanism of mitochondrial complex I
Respiratory complex I plays a key role in energy metabolism. Cryo-EM structure of a mutant accessory subunit LYRM6 from the yeast Yarrowia lipolytica and molecular dynamics simulations reveal conformational changes at the interface between LYRM6 and subunit ND3, propagated further into the complex. These findings offer insight into the mechanism of proton pumping by respiratory complex I.
- Etienne Galemou Yoga
- , Kristian Parey
- & Heike Angerer
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Article
| Open AccessStructure of inhibitor-bound mammalian complex I
The respiratory complex I (NADH:ubiquinone oxidoreductase) is a large redox-driven proton pump that initiates respiration in mitochondria. Here, the authors present the 3.0 Å cryo-EM structure of complex I from mouse heart mitochondria with the ubiquinone-analogue inhibitor piericidin A bound in the active site and with kinetic measurements and MD simulations they further show that this inhibitor acts competitively against the native ubiquinone-10 substrate.
- Hannah R. Bridges
- , Justin G. Fedor
- & Judy Hirst
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Article
| Open AccessStructural basis for energy transfer in a huge diatom PSI-FCPI supercomplex
Diatoms are marine algae with an important role in global photosynthetic carbon fixation. Here, the authors present the 2.38 Å cryo-EM structure of photosystem I (PSI) in complex with its 24 fucoxanthin chlorophyll a/c-binding (FCPI) antenna proteins from the diatom Chaetoceros gracilis, which provides mechanistic insights into light-energy harvesting, transfer and quenching of the PSI-FCPI supercomplex.
- Caizhe Xu
- , Xiong Pi
- & Jian-Ren Shen
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Article
| Open AccessMonitoring and modeling of lymphocytic leukemia cell bioenergetics reveals decreased ATP synthesis during cell division
ATP drives most cellular processes, although ATP production and consumption levels during mitosis remain unreported. Here, the authors combine metabolic measurements and modeling to quantify ATP levels and synthesis dynamics, revealing that ATP synthesis and consumption are lowered during mitosis.
- Joon Ho Kang
- , Georgios Katsikis
- & Teemu P. Miettinen
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Article
| Open AccessArrangement and symmetry of the fungal E3BP-containing core of the pyruvate dehydrogenase complex
The pyruvate dehydrogenase complex (PDC) is a multienzyme complex connecting glycolysis to mitochondrial oxidation of pyruvate. Cryo-EM analysis of PDC from Neurospora crassa reveals localization of fungi-specific protein X (PX) and confirms that it functions like the mammalian E3BP, recruiting the E3 component of PDC.
- B. O. Forsberg
- , S. Aibara
- & E. Lindahl
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Article
| Open AccessKey role of quinone in the mechanism of respiratory complex I
Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the respiratory chain in bacteria and mitochondria. Here, the authors present cryo-EM and crystal structures of T. thermophilus complex I in different conformational states and further analyse them by Normal Mode Analysis and molecular dynamics simulations and conclude that quinone redox reactions are important for the coupling mechanism of complex I.
- Javier Gutiérrez-Fernández
- , Karol Kaszuba
- & Leonid A. Sazanov
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Article
| Open AccessCryo-EM structures provide insight into how E. coli F1Fo ATP synthase accommodates symmetry mismatch
F1Fo ATP synthase consists of two coupled rotary molecular motors: the soluble ATPase F1 and the transmembrane Fo. Here, the authors present cryo-EM structures of E. coli ATP synthase in four discrete rotational sub-states at 3.1-3.4 Å resolution and observe a rotary sub-step of the Fo motor cring that reveals the mechanism of elastic coupling between the two rotary motors, which is essential for effective ATP synthesis.
- Meghna Sobti
- , James L. Walshe
- & Alastair G. Stewart
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Article
| Open AccessStructural insights into catalytic mechanism and product delivery of cyanobacterial acyl-acyl carrier protein reductase
Acyl-acyl carrier protein reductase (AAR) and aldehyde deformylating oxygenase (ADO) are the two enzymes in a cyanobacterial alkane biosynthesis pathway that is of interest for biofuel production. Here the authors provide insights into the catalytic mechanisms of AAR and the coupling between the two enzymes by determining the crystal structures of AAR alone and three AAR–ADO complexes with various bound ligands.
- Yu Gao
- , Hongmei Zhang
- & Mei Li
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Article
| Open AccessCharge transfer from the carotenoid can quench chlorophyll excitation in antenna complexes of plants
The plant photosynthetic machinery quenches excess excitation energy to avoid photodamage. Here, via molecular dynamics and quantum chemical calculations, Cupellini et al. show that lutein/chlorophyll pairs in light-harvesting complex II can quench excess energy via a transient charge transfer state.
- Lorenzo Cupellini
- , Dario Calvani
- & Benedetta Mennucci
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Article
| Open AccessPhysical and behavioral adaptations to prevent overheating of the living wings of butterflies
Butterfly wings have low thermal capacity and thus are vulnerable to damage by overheating. Here, Tsai et al. take an interdisciplinary approach to reveal the organs, nanostructures and behaviors that enable butterflies to sense and regulate their wing temperature.
- Cheng-Chia Tsai
- , Richard A. Childers
- & Nanfang Yu
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Article
| Open AccessPurified F-ATP synthase forms a Ca2+-dependent high-conductance channel matching the mitochondrial permeability transition pore
The molecular identity of the mitochondrial megachannel (MMC)/permeability transition pore (PTP), a key effector of cell death, remains controversial. Here authors demonstrate that the membrane embedded bovine F-ATP synthase elicits Ca2 + -dependent currents matching those of the MMC/PTP.
- Andrea Urbani
- , Valentina Giorgio
- & Paolo Bernardi