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| Open AccessDNA unwinding mechanism of a eukaryotic replicative CMG helicase
The DNA duplex is known to be split apart in a steric exclusion manner during replication, but the specific mechanism has remained unclear. Here the authors present a cryo-EM structure of a eukaryotic replicative CMG helicase on forked DNA, revealing the mechanism of DNA unwinding.
- Zuanning Yuan
- , Roxana Georgescu
- & Michael E. O’Donnell
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Article
| Open AccessStructural basis of proton-coupled potassium transport in the KUP family
KUP transporters facilitate potassium uptake by the co-transport of protons and are key players in potassium homeostasis. Here authors identify the potassium importer KimA from Bacillus subtilis as a new member of the KUP transporter family and show the cryo-EM structure of KimA in an inward-occluded, trans-inhibited conformation.
- Igor Tascón
- , Joana S. Sousa
- & Inga Hänelt
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Article
| Open AccessStructural basis for electron transport mechanism of complex I-like photosynthetic NAD(P)H dehydrogenase
NAD(P)H dehydrogenase-like complex NDH-1L couples the electron transport from ferredoxin (Fd) to plastoquinone (PQ) and proton pumping from cytoplasm to the lumen. Here authors report two structures of NDH-1L from Thermosynechococcus elongatus BP-1, in complex with one Fd and an endogenous PQ, respectively.
- Xiaowei Pan
- , Duanfang Cao
- & Mei Li
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Article
| Open AccessRobust ultraclean atomically thin membranes for atomic-resolution electron microscopy
High-resolution electron microscopy requires robust and noise-free substrates to support the specimens. Here, the authors present a polymer- and transfer-free direct-etching method for fabrication of graphene grids with ultraclean surfaces and demonstrate cryo-EM at record high resolution.
- Liming Zheng
- , Yanan Chen
- & Hailin Peng
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Article
| Open AccessTrkA undergoes a tetramer-to-dimer conversion to open TrkH which enables changes in membrane potential
TrkH is a bacterial ion channel that is regulated by nucleotides and its associated protein TrkA. Here the authors present ADP and ATP bound TrkH-TrkA structures, which reveal the mechanism for the transmission of nucleotide-induced conformational changes in TrkA to the opening of the TrkH channel and further support the proposed gating mechanism with functional studies.
- Hanzhi Zhang
- , Yaping Pan
- & Ming Zhou
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Article
| Open AccessDisruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements
Here, using cryo-EM and smFRET, Henderson et al. show how tryptophan 571 in the HIV-1 Env acts as a conformational switch during receptor-mediated viral entry and design HIV-1 Env proteins that cannot undergo conformational changes. This has important implications for HIV-1 vaccine design.
- Rory Henderson
- , Maolin Lu
- & S. Munir Alam
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Article
| Open AccessRedox-coupled proton pumping drives carbon concentration in the photosynthetic complex I
Cyanobacteria evolved carbon-concentration mechanisms to enhance the efficiency of photosynthetic CO2 fixation, but the molecular principles have remained unknown. Here authors use cryo-EM to reveal how modular adaptations enabled the photosynthetic complex I from the cyanobacterium Thermosynechococcus elongatus to concentrate CO2.
- Jan M. Schuller
- , Patricia Saura
- & Ville R. I. Kaila
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Article
| Open AccessStructural basis of p62/SQSTM1 helical filaments and their role in cellular cargo uptake
PB1-mediated oligomerization of p62/SQSTM1 is essential for its function as a selective autophagy receptor. Here the authors present the cryo-EM structures of human and Arabidopsis PB1 domain helical assemblies and find that a conserved double arginine finger in the PB1 domain is important for p62 polymerisation and lysosomal targeting of p62.
- Arjen J. Jakobi
- , Stefan T. Huber
- & Carsten Sachse
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Article
| Open AccessEncapsulation mechanisms and structural studies of GRM2 bacterial microcompartment particles
Bacterial microcompartments (BMCs) consist of a protein shell and an encapsulated enzymatic core. Here, Kalnins et al. study a BMC from Klebsiella pneumoniae, show that the enzymatic core is encapsulated in a hierarchical manner, and solve the cryo-EM structure of a pT = 4 quasi-symmetric icosahedral shell particle.
- Gints Kalnins
- , Eva-Emilija Cesle
- & Kaspars Tars
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Article
| Open AccessCryo-EM structure of the respiratory syncytial virus RNA polymerase
Respiratory syncytial virus (RSV) is a pathogenic non-segmented negative-sense RNA virus and active RSV polymerase is composed of a 250 kDa large (L) protein and tetrameric phosphoprotein (P). Here, the authors present the 3.67 Å cryo-EM structure of the RSV polymerase (L:P) complex.
- Dongdong Cao
- , Yunrong Gao
- & Bo Liang
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Article
| Open AccessAssembly and substrate recognition of curli biogenesis system
A major component of bacterial biofilms is curli amyloid fibrils secreted by the curli biogenesis system. Here authors use cryo-EM to visualize the secretion channel complexes (CsgF-CsgG) with and without the curli substrate and provide insights into curli biogenesis.
- Zhaofeng Yan
- , Meng Yin
- & Xueming Li
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Article
| Open AccessNested helicoids in biological microstructures
Helicoids are common structures found in many structural biological materials. Here, the authors report on a study of helicoids in the claws of scorpions and report different microstructures to what have previously been reported which have implications in materials stiffness, strength and toughness.
- Israel Greenfeld
- , Israel Kellersztein
- & H. Daniel Wagner
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Article
| Open AccessStructural basis for the adaptation and function of chlorophyll f in photosystem I
Chlorophyll f (Chl f) is the most red-shifted Chl in oxygenic photosynthesis but its localization in photosystem I (PSI) has been unknown so far. Here the authors determine the cryo-EM structures of PSI complexes from a Chl f-containing cyanobacterium grown either under white light or far-red light conditions and identify seven Chls f in the far-red light PSI structure, whereas PSI from cells grown under white light contains only Chl a.
- Koji Kato
- , Toshiyuki Shinoda
- & Tatsuya Tomo
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Article
| Open AccessCardiac muscle thin filament structures reveal calcium regulatory mechanism
The contraction of cardiac and skeletal muscles is regulated by Ca2+ released from the sarcoplasmic reticulum in muscle cells. Here the authors provide molecular insights into Ca2+ regulation of muscle contraction by determining the cryo-EM structures of the human cardiac muscle thin filament in the absence and presence of Ca2+.
- Yurika Yamada
- , Keiichi Namba
- & Takashi Fujii
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Article
| Open AccessHand-foot-and-mouth disease virus receptor KREMEN1 binds the canyon of Coxsackie Virus A10
Here, the authors provide the structure of mature Coxsackie Virus A10 alone and in complex with its receptor KREMEN1, and of A-particles. This shows how the receptor spans the viral canyon and suggests that receptor binding triggers pocket factor release and conformational changes resulting in expanded particles.
- Yuguang Zhao
- , Daming Zhou
- & David I. Stuart
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Article
| Open AccessMeasuring local-directional resolution and local anisotropy in cryo-EM maps
It is important to analyse the local resolution of cryo-EM maps. Here the authors present MonoDir, a fully automatic and parameter free method for the directional local resolution analysis of cryo-EM maps that requires only the final map as input and they also propose indicators for assessing map quality.
- Jose Luis Vilas
- , Hemant D. Tagare
- & Carlos Oscar S. Sorzano
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Article
| Open AccessDirect observation of dynamic protein interactions involving human microtubules using solid-state NMR spectroscopy
Microtubule (MT) organization is regulated by many microtubule-associated proteins (MAPs) that contain intrinsically disordered regions. Here authors produce [13C, 15N] labeled, functional microtubules from human cells for solid-state NMR which allows studying MAP-MT interactions.
- Yanzhang Luo
- , ShengQi Xiang
- & Marc Baldus
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Article
| Open AccessStructural basis for Fullerene geometry in a human endogenous retrovirus capsid
In retroviruses, the capsid protein (CA) forms a shell surrounding the viral core. Here the authors combine cryo-electron microscopy with NMR and X-ray crystallography to examine the CA structure from the human endogenous retrovirus HML2 (HERV-K) and determine the structures of four Fullerene CA closed shells that reveal the molecular basis of capsid assembly.
- Oliver Acton
- , Tim Grant
- & Peter B. Rosenthal
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Article
| Open AccessStructural basis of nucleosome assembly by the Abo1 AAA+ ATPase histone chaperone
ATAD2 AAA+ ATPases are a family of histone chaperones that regulate nucleosome density and chromatin dynamics. Here, authors find that the fission yeast ATAD2 homolog Abo1 deposits histone H3–H4 onto DNA in an ATP-hydrolysis-dependent manner, and present the cryo-EM structure of an ATAD2 family ATPase to reveal the structural basis of nucleosome assembly by Abo1.
- Carol Cho
- , Juwon Jang
- & Ji-Joon Song
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Article
| Open AccessCryo-EM structure of the human MLL1 core complex bound to the nucleosome
MLL family histone methyltransferases deposit histone H3 Lys4 mono-/di-/tri-methylation and regulate gene expression in mammals. Here the authors report the single-particle cryo-EM structure of the NCP-bound human MLL1 core complex, shedding light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity.
- Sang Ho Park
- , Alex Ayoub
- & Uhn-Soo Cho
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Article
| Open AccessMolecular insight into RNA polymerase I promoter recognition and promoter melting
RNA polymerase I (Pol I) catalyses the transcription of pre-ribosomal RNA and for transcription initiation Pol I assembles with core factor and Rrn3 on the rDNA core promoter. Here the authors provide insights into the molecular mechanism of promoter opening by Pol I by determining the cryo-EM structures of two closed, two intermediate and two open Pol I pre-initiation complexes.
- Yashar Sadian
- , Florence Baudin
- & Christoph W. Müller
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Article
| Open AccessCryo-EM structure of a 40 kDa SAM-IV riboswitch RNA at 3.7 Å resolution
The conformational heterogeneity of RNA molecules makes their structure determination by X-ray crystallography and NMR challenging. Here the authors show that RNA structures can be solved by cryo-EM and present the structures of a 40 kDa SAM-IV riboswitch in the apo form and bound to its ligand S-adenosylmethionine.
- Kaiming Zhang
- , Shanshan Li
- & Wah Chiu
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Article
| Open AccessCore architecture of a bacterial type II secretion system
Bacterial type II secretion systems (T2SSs) translocate virulence factors, toxins and enzymes across the cell outer membrane. Here, Chernyatina and Low use negative stain and cryo-electron microscopy to reveal the core architecture of an assembled T2SS from the pathogen Klebsiella pneumoniae.
- Anastasia A. Chernyatina
- & Harry H. Low
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Article
| Open AccessAtomic structure of the human herpesvirus 6B capsid and capsid-associated tegument complexes
Human Herpesvirus 6B (HHV-6) can cause fever, diarrhea and roseola rash. Here the authors present a cryoEM approach to image crude, minimally purified virus samples and employ it to determine the atomic structures of HHV-6B capsid and capsid-associated tegument protein complexes.
- Yibo Zhang
- , Wei Liu
- & Z. Hong Zhou
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Article
| Open AccessStructure of the native supercoiled flagellar hook as a universal joint
The bacterial flagellar hook is a molecular universal joint that connects the rotary motor and long helical propeller of the bacterial flagellum. Here the authors present the 3.6 Å resolution cryo-EM structure of the native supercoiled Salmonella hook that provides insights into the dynamic changes of subunit conformations and intermolecular interactions of the hook protein FlgE.
- Takayuki Kato
- , Fumiaki Makino
- & Keiichi Namba
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Article
| Open AccessStructural determinants of microtubule minus end preference in CAMSAP CKK domains
CKK domain containing CAMSAP/Patronins recognise and regulate microtubule (MT) minus end dynamics. Here the authors compare cryo-EM structures of MT-bound human CKK and Naegleria gruberi CKK which lacks minus-end binding preference, finding NgCKK has a different interaction with, and inability to remodel, its MT binding site, shedding light on the CAMSAP/Patronin end binding mechanism.
- Joseph Atherton
- , Yanzhang Luo
- & Carolyn A. Moores
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Article
| Open AccessTowards the application of Tc toxins as a universal protein translocation system
Tc toxins are a major class of bacterial toxin translocation systems that inject toxic enzymes into target cells. Here the authors present functional and structural data showing that the toxic enzyme can be replaced by other small proteins and identify prerequisites required for successful translocation, which could facilitate the development of functional Tc-based protein injection devices.
- Daniel Roderer
- , Evelyn Schubert
- & Stefan Raunser
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Article
| Open AccessMultiple conformations facilitate PilT function in the type IV pilus
Bacterial type IV pilus-like systems catalyse the formation of pilin fibres but it is unknown how they are powered. Here, the authors present crystal and cryo-EM structures of the hexameric motor ATPases PilB and PilT from Type IVa Pilus that reveal different conformational states, classify the conformations of all PilT-like ATPase structures and propose a model for PilT function.
- Matthew McCallum
- , Samir Benlekbir
- & P. Lynne Howell
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Article
| Open AccessHomologous bd oxidases share the same architecture but differ in mechanism
Cytochrome bd oxidases couple quinol oxidation and the release of protons to the periplasmic side with proton uptake from the cytoplasmic side to reduce dioxygen to water and they are the terminal reductases in bacterial and archaeal respiratory chains. Here the authors present the cryo-EM structure of Escherichia coli bd oxidase and discuss mechanistic implications.
- Alexander Theßeling
- , Tim Rasmussen
- & Thorsten Friedrich
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Article
| Open AccessCryo-EM structure of a transthyretin-derived amyloid fibril from a patient with hereditary ATTR amyloidosis
Systemic amyloidosis of the ATTR is one of the most abundant forms of systemic amyloidosis and caused by misfolding of the circulating blood protein transthyretin (TTR). Here the authors present the cryo-EM structure of patient-derived Val30Met ATTR amyloid fibrils which reveals that the protofilament consists of an N-terminal and a C-terminal TTR fragment and discuss implications for the mechanism of misfolding.
- Matthias Schmidt
- , Sebastian Wiese
- & Marcus Fändrich
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Article
| Open AccessStructure of a cyanobacterial photosystem I tetramer revealed by cryo-electron microscopy
Photosystem I (PSI) is embedded in thylakoid membranes of photosynthetic organisms, converting light energy into chemical energy, and its oligomeric state varies among different organisms. Here the authors present the 3.3 Å resolution cryo-EM structure of the PSI tetramer from the cyanobacterium Anabaena sp. PCC 7120.
- Koji Kato
- , Ryo Nagao
- & Fusamichi Akita
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Article
| Open AccessCryo-EM structure of the complete E. coli DNA gyrase nucleoprotein complex
Bacterial DNA gyrase is the only type II DNA topoisomerase capable of introducing negative supercoils into DNA and is of interest as a drug target. Here the authors present the cryo-EM structure of the complete E. coli DNA gyrase bound to a 180 bp double-stranded DNA and the antibiotic gepotidacin, which reveals the connections between the functional domains and their spatial organization.
- Arnaud Vanden Broeck
- , Christophe Lotz
- & Valérie Lamour
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Article
| Open AccessCryo-EM structure and polymorphism of Aβ amyloid fibrils purified from Alzheimer’s brain tissue
Alzheimer’s disease is characterised by the deposition of Aβ amyloid fibrils and tau protein neurofibrillary tangles. Here the authors use cryo-EM to structurally characterise brain derived Aβ amyloid fibrils and find that they are polymorphic and right-hand twisted, which differs from in vitro generated Aβ fibrils.
- Marius Kollmer
- , William Close
- & Marcus Fändrich
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Article
| Open AccessStructural transitions during the scaffolding-driven assembly of a viral capsid
Viral assembly is a complex process that in tailed bacteriophages involves scaffolding proteins which coordinate assembly of the phage procapsid and are subsequently released during maturation. Here the authors reveal the conformational changes that accompany virion maturation, documenting how the dissociation of scaffold proteins and DNA packaging processes intersect.
- Athanasios Ignatiou
- , Sandrine Brasilès
- & Elena V. Orlova
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Article
| Open AccessStructure of ribosome-bound azole-modified peptide phazolicin rationalizes its species-specific mode of bacterial translation inhibition
The authors report the identification of phazolicin (PHZ) - a prokaryotic translation inhibitory peptide - and its structure in complex with the E. coli ribosome, delineating PHZ’s mode of action and suggesting a basis for its bacterial species-specific activity.
- Dmitrii Y. Travin
- , Zoe L. Watson
- & Konstantin Severinov
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Article
| Open AccessStructural basis of the activation of type 1 insulin-like growth factor receptor
The activation mechanism of type 1 insulin-like growth factor receptor (IGF1R) is not fully understood. Here, the authors determine the cryo-EM structure of full-length, IGF1-bound IGF1R in the active conformation, providing insights into how IGF1 triggers receptor activation.
- Jie Li
- , Eunhee Choi
- & Xiao-chen Bai
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Article
| Open AccessAldehyde-alcohol dehydrogenase forms a high-order spirosome architecture critical for its activity
Aldehyde-alcohol dehydrogenase (AdhE) converts acetyl-CoA to ethanol and plays an important role in bacterial fermentation. Here the authors present the 3.5 Å cryo-EM structure of full-length E. coli AdhE, which reveals a right-handed helical spirosome structure and they show that the helical structure is required for AdhE activity.
- Gijeong Kim
- , Liyana Azmi
- & Ji-Joon Song
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Article
| Open AccessPrinciples for enhancing virus capsid capacity and stability from a thermophilic virus capsid structure
Viral capsids need to protect the genome against harsh environmental conditions and cope with high internal pressure from the packaged genome. Here, the authors determine the structure of the thermostable phage P74-26 capsid at 2.8-Å resolution and identify features underlying enhanced capsid capacity and structural stability.
- Nicholas P. Stone
- , Gabriel Demo
- & Brian A. Kelch
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Article
| Open AccessStructure of Csx1-cOA4 complex reveals the basis of RNA decay in Type III-B CRISPR-Cas
Type III CRISPR-Cas RNases from the Csm and Csx families are activated by cyclic oligoadenylates (cOA). Here the authors present the cOA bound Sulfolobus islandicus Csx1 structure, which forms a hexamer and reveal an allosteric mechanism for the activation of Csx1 RNase.
- Rafael Molina
- , Stefano Stella
- & Guillermo Montoya
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Article
| Open AccessThe cryo-EM structure of the acid activatable pore-forming immune effector Macrophage-expressed gene 1
Macrophage-expressed gene 1 (MPEG1) functions within the phagolysosome to damage engulfed microbes, presumably via forming pores in target membranes. In order to provide insights into the mechanism of MPEG1 function and membrane binding, the authors present structures of hexadecameric MPEG1 prepores both in solution and in complex with liposomes.
- Siew Siew Pang
- , Charles Bayly-Jones
- & James C. Whisstock
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Article
| Open AccessRetroviral integration into nucleosomes through DNA looping and sliding along the histone octamer
Retroviral integrases catalyze the insertion of viral DNA into the host cell DNA and can use nucleosomes as substrates for integration. Here the authors present the 3.9 Å cryo-EM structure of prototype foamy virus integrase after strand transfer into nucleosomal DNA, which together with single-molecule FRET measurements provides evidence for a DNA looping and sliding mechanism of integrases.
- Marcus D. Wilson
- , Ludovic Renault
- & Alessandro Costa
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Article
| Open AccessCryo-EM structures of lipopolysaccharide transporter LptB2FGC in lipopolysaccharide or AMP-PNP-bound states reveal its transport mechanism
Seven lipopolysaccharide (LPS) transport proteins (LptBFGCADE) mediate the transport of LPS from the inner to the outer membrane of Gram-negative bacteria. Here the authors provide mechanistic insights into LPS recognition and transportation by determining the cryo-EM structures of the inner membrane complex LptB2FGC bound to either LPS or AMP-PNP.
- Xiaodi Tang
- , Shenghai Chang
- & Haohao Dong
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Article
| Open AccessStructure of the thermo-sensitive TRP channel TRP1 from the alga Chlamydomonas reinhardtii
Transient receptor potential (TRP) channels are ubiquitous occurring cation-selective sensory ion channels that respond to various stimuli. Here the authors characterize crTRP1 from the alga Chlamydomonas reinhardtii, present its 3.5 Å cryo-EM structure and show that crTRP1 opens in response to increased temperature and is positively regulated by the membrane lipid PIP2.
- Luke L. McGoldrick
- , Appu K. Singh
- & Alexander I. Sobolevsky
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Article
| Open AccessAutoinhibition and activation mechanisms of the eukaryotic lipid flippase Drs2p-Cdc50p
The heterodimeric eukaryotic Drs2p-Cdc50p complex is a lipid flippase that maintains cell membrane asymmetry and its autoinhibition is released by PI4P binding. Here authors show cryo-EM structures of Drs2p-Cdc50p in apo and PI4P-activated form which reveal the structural changes upon PI4P binding.
- Lin Bai
- , Amanda Kovach
- & Huilin Li
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Article
| Open AccessMolecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway
The bacterial enzyme PaaZ is involved in the breakdown of environmental pollutants via the aerobic-anaerobic hybrid pathway but its substrate transfer mechanism is not fully understood. Here, the authors present cryoEM structures of free and ligand-bound PaaZ that suggest a mechanism for internal substrate channeling.
- Nitish Sathyanarayanan
- , Giuseppe Cannone
- & Kutti R. Vinothkumar
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Article
| Open AccessCryoEM structures of Arabidopsis DDR complexes involved in RNA-directed DNA methylation
RNA polymerase V transcription in plants, which is needed DNA methylation and transcriptional silencing, requires components of the DDR complex. Here the authors show that all components of the DDR complex co-localize with Pol V and report the cryoEM structures of two complexes associated with Pol V recruitment.
- Somsakul Pop Wongpalee
- , Shiheng Liu
- & Steven E. Jacobsen
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Article
| Open AccessThe structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K
TMEM16K is a member of the TMEM16 family of integral membrane proteins that are either lipid scramblases or chloride channels. Here the authors combine cell biology, electrophysiology measurements, X-ray crystallography, cryo-EM and MD simulations to structurally characterize TMEM16K and show that it is an ER-resident lipid scramblase.
- Simon R. Bushell
- , Ashley C. W. Pike
- & Elisabeth P. Carpenter
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Article
| Open AccessAtomic structure of the Epstein-Barr virus portal
The Epstein-Barr virus (EBV) is a dangerous human pathogen responsible for mononucleosis and several types of cancers. Here the authors describe a high-resolution atomic structure of the EBV portal, which serves as the entrance and exit pore for the viral genome and is a potential pharmacological target for the development of antivirals.
- Cristina Machón
- , Montserrat Fàbrega-Ferrer
- & Miquel Coll
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Article
| Open AccessCyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C
During the spindle assembly checkpoint, the activity of the anaphase promoting complex/cyclosome (APC/C) is repressed, yet cyclin A2 evades the checkpoint and is targeted for degradation. Here, the authors define the underlying mechanism and reveal that cyclin A2 engages the APC/C in multiple binding modes.
- Suyang Zhang
- , Thomas Tischer
- & David Barford