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| Open AccessCryo-EM structure of a licensed DNA replication origin
Origins of replication are licensed by loading of MCM onto DNA, and origin firing depends on interaction with Cdc45 and GINS to form two CMG holo-helicases. Here, authors determine the cryo-EM structures of DNA-bound MCM and visualise a phospho-dependent MCM element important for Cdc45 recruitment.
- Ferdos Abid Ali
- , Max E. Douglas
- & Alessandro Costa
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Article
| Open AccessCatastrophic disassembly of actin filaments via Mical-mediated oxidation
MICAL Redox enzymes post-translationally modify F-actin to promote its cellular destabilization. Here, the authors present a 3.9Å cryoEM structure of Mical-oxidized F-actin, showing its nucleotide-state dependent dynamic instability and susceptibility to cofilin-induced severing in the presence of inorganic phosphate.
- Elena E. Grintsevich
- , Peng Ge
- & Emil Reisler
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Article
| Open AccessNucleotide– and Mal3-dependent changes in fission yeast microtubules suggest a structural plasticity view of dynamics
Microtubules are vital and highly conserved components of the cytoskeleton. Here the authors carry out a structural analysis of fission yeast microtubules in the presence and absence of the microtubule end-binding protein Mal3 that demonstrates structural plasticity amongst microtubule polymers.
- Ottilie von Loeffelholz
- , Neil A. Venables
- & Carolyn A. Moores
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Article
| Open AccessBri2 BRICHOS client specificity and chaperone activity are governed by assembly state
The BRICHOS domain is a chaperone that can act against amyloid-β peptide fibril formation and non-fibrillar protein aggregation. Here the authors use a multidisciplinary approach and show that the Bri2 BRICHOS domain has qualitatively different chaperone activities depending on its quaternary structure.
- Gefei Chen
- , Axel Abelein
- & Jan Johansson
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Article
| Open AccessInsights into the structure and assembly of a bacterial cellulose secretion system
Many Gram-negative bacteria secrete exopolysaccharides via functionally homologous synthase-dependent systems. Here the authors use electron microscopy to reveal that biofilm-promoting cellulose in E. coli is secreted by a conserved multi-component secretion system with a megadalton-sized asymmetric architecture.
- Petya Violinova Krasteva
- , Joaquin Bernal-Bayard
- & Jean-Marc Ghigo
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Article
| Open AccessBacteriophage T5 tail tube structure suggests a trigger mechanism for Siphoviridae DNA ejection
Host cell recognition is mediated by the phage tail tip proteins, which then triggers viral genome delivery via the phage tail. Here, the authors combine crystallography and cryoEM to structurally characterise the bacteriophage T5 tail tube structure before and after interaction with its host receptor.
- Charles-Adrien Arnaud
- , Grégory Effantin
- & Cécile Breyton
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Article
| Open AccessCryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2
Target of rapamycin (TOR) kinase operates within two distinct multiprotein complexes named TORC1 and TORC2. Here the authors report a cryo-EM structure of TORC2, establish its subunit organization, providing a rationale for TORC2’s rapamycin insensitivity and the mutually exclusive inclusion of Avo3/Rictor or Raptor within their respective TOR complex.
- Manikandan Karuppasamy
- , Beata Kusmider
- & Christiane Schaffitzel
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Article
| Open AccessStructure of human immunoproteasome with a reversible and noncompetitive inhibitor that selectively inhibits activated lymphocytes
Immunoproteasome selective inhibitors might lead to less toxic drugs for treatment of multiple myeloma and graft rejection. Here, the authors develop immunoproteasome specific asparagine-ethylenediamine (AsnEDA)-based inhibitory compounds, demonstrate their efficacy and present the AsnEDA bound immunoproteasome cryo-EM structure.
- Ruda de Luna Almeida Santos
- , Lin Bai
- & Gang Lin
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Article
| Open AccessAtomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin
Leishmaniasis is a parasitic disease transmitted by the bite of infected sand flies. Here the authors describe an atomic resolution cryo-EM structure of the Leishmania ribosome in complex with the recently approved drug paromomycin (PAR) and highlight conserved elements in the drug binding pocket that mediate PAR deleterious effects on the parasite.
- Moran Shalev-Benami
- , Yan Zhang
- & Georgios Skiniotis
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Article
| Open AccessStructure of the transcription activator target Tra1 within the chromatin modifying complex SAGA
The transcription co-activator complex SAGA is recruited to promoters by transcriptional activators and promotes the formation of the pre-initiation complex. Here, the authors present the cryo-EM structure of the SAGA complex and resolve the major target of activator binding, the 430 kDa Tra1 protein.
- Grigory Sharov
- , Karine Voltz
- & Patrick Schultz
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Article
| Open AccessStructural basis for tRNA-dependent cysteine biosynthesis
tRNA-dependent cysteine biosynthesis is catalyzed by the transsulfursome protein complex. Here, the authors use a multidisciplinary approach to structurally characterize the archaeal transsulfursome and propose a model for tRNA channeling in the complex.
- Meirong Chen
- , Koji Kato
- & Min Yao
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Article
| Open AccessUnique architecture of thermophilic archaeal virus APBV1 and its genome packaging
The rod-shaped virus APBV1 is among the most thermostable viruses known. Here, Ptchelkine et al. determine its structure at near-atomic resolution, show that the DNA is packed as left-handed superhelix and identify extended hydrophobic interfaces that likely contribute to the extreme thermostability of the capsid.
- Denis Ptchelkine
- , Ashley Gillum
- & Juha T. Huiskonen
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Article
| Open AccessStructural insights into DNA cleavage activation of CRISPR-Cas9 system
CRISPR-Cas9 is widely used for genome engineering but structural data for the DNA cleavage step are still incomplete. Here, the authors present the cryo-EM structure of a ternary Cas9-sgRNA-target DNA complex, perform MD simulations and discuss implications for the Cas9 DNA cleavage mechanism.
- Cong Huai
- , Gan Li
- & Qiang Huang
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Article
| Open AccessStructural basis for high-affinity actin binding revealed by a β-III-spectrin SCA5 missense mutation
The disease causing L253P mutation in the actin-binding domain (ABD) of β-III-spectrin drastically increases actin-binding affinity. Here, the authors present the cryo-EM structure of F-actin complexed with the ABD mutant and double electron–electron resonance measurements show how the mutation affects the ABD conformational state.
- Adam W. Avery
- , Michael E. Fealey
- & Edward H. Egelman
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Article
| Open AccessThe structural basis of proton driven zinc transport by ZntB
The bacterial zinc transporter ZntB is important for maintaining zinc homeostasis and is mechanistically not well understood. Here, the authors present the cryo-EM structure of ZntB at 4.2 Å resolution, perform transport assays and propose a model for its Zn2+ transport mechanism.
- Cornelius Gati
- , Artem Stetsenko
- & Albert Guskov
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Article
| Open AccessCryoEM structure of Saccharomyces cerevisiae U1 snRNP offers insight into alternative splicing
U1 snRNP is critical for 5′ splicing site recognition in pre-mRNA splicing. Here the authors describe the cryo-EM structure of the yeast U1 snRNP and suggest that PrpF39 is an alternative splicing factor essential for the successful recruitment of U1 snRNP by other alternative splicing factors.
- Xueni Li
- , Shiheng Liu
- & Rui Zhao
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Article
| Open AccessA structural model of flagellar filament switching across multiple bacterial species
Bacterial flagellar filaments are composed almost entirely of a single protein—flagellin—which can switch between different supercoiled states in a highly cooperative manner. Here the authors present near-atomic resolution cryo-EM structures of nine flagellar filaments, and begin to shed light on the molecular basis of filament switching.
- Fengbin Wang
- , Andrew M. Burrage
- & Edward H. Egelman
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Article
| Open AccessMolecular basis of human CD22 function and therapeutic targeting
The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells. Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.
- June Ereño-Orbea
- , Taylor Sicard
- & Jean-Philippe Julien
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| Open AccessA general mechanism of ribosome dimerization revealed by single-particle cryo-electron microscopy
When bacteria enter the stationary growth phase, protein translation is suppressed via the dimerization of 70S ribosomes into inactive complexes. Here the authors provide a structural basis for how the dual domain hibernation promotion factor promotes ribosome dimerization and hibernation in bacteria.
- Linda E. Franken
- , Gert T. Oostergetel
- & Albert Guskov
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| Open AccessThe cryo-EM structure of hibernating 100S ribosome dimer from pathogenic Staphylococcus aureus
Under conditions of nutrient limitation, bacterial ribosomes undergo dimerization, forming a 100S complex that is translationally inactive. Here the authors present the structural basis for formation of the 100S complexes in Gram-positive bacteria, shedding light on the mechanism of translation suppression by the ribosome-silencing factors.
- Donna Matzov
- , Shintaro Aibara
- & Ada E. Yonath
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| Open AccessMeasuring the effects of particle orientation to improve the efficiency of electron cryomicroscopy
A number of parameters influence the resolution of a cryo-EM structure. Here the authors investigate the effects of specimen orientation in single particle cryo-EM and present open-source software for rapidly assessing orientation distributions to improve data collection.
- Katerina Naydenova
- & Christopher J. Russo
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Article
| Open AccessAtomic structures of Coxsackievirus A6 and its complex with a neutralizing antibody
Coxsackievirus A6 (CVA6) causes hand, foot and mouth disease in children. Here the authors present the CVA6 procapsid and A-particle cryo-EM structures and identify an immune-dominant neutralizing epitope, which can be exploited for vaccine development.
- Longfa Xu
- , Qingbing Zheng
- & Ningshao Xia
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Article
| Open AccessCryo-EM structures of the ATP-bound Vps4E233Q hexamer and its complex with Vta1 at near-atomic resolution
The ESCRT-III and Vps4 complexes mediate a variety of membrane remodelling events. Here the authors describe the structure of the Vps4 hexamer complexed to its cofactor Vta1, and show that Vta1 bridges adjacent Vps4 subunits to promote formation of the active hexamer during ESCRT-III filament disassembly.
- Shan Sun
- , Lin Li
- & Sen-Fang Sui
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Article
| Open AccessCryo-EM structure of haemoglobin at 3.2 Å determined with the Volta phase plate
Single particle cryo-EM is commonly used for the structure determination of large complexes. Here, the authors present the 3.2 Å resolution cryo-EM structure of human haemoglobin, which has a molecular weight of 64 kDa.
- Maryam Khoshouei
- , Mazdak Radjainia
- & Radostin Danev
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Article
| Open AccessCdt1 stabilizes an open MCM ring for helicase loading
The loading and activation of the Mcm2-7 replicative helicase couples cell cycle progression to DNA replication. Here the authors use X-ray crystallography and single-particle electron microscopy to demonstrate how Ctd1 functions to promote MCM loading onto DNA.
- Jordi Frigola
- , Jun He
- & John F. X. Diffley
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Article
| Open AccessPlastid thylakoid architecture optimizes photosynthesis in diatoms
Phytoplankton and plant plastids have distinct evolutionary origins and membrane organization. Here Floriet al. show that diatom photosynthetic complexes spatially segregate into interconnected subdomains within loose thylakoid stacks enabling fast diffusion of electron carriers and efficient photosynthesis
- Serena Flori
- , Pierre-Henri Jouneau
- & Giovanni Finazzi
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Article
| Open AccessThe CaMKII holoenzyme structure in activation-competent conformations
Ca2+/calmodulin-dependent protein kinase II (CaMKII) forms a 12 subunit holoenzyme central to synaptic plasticity. Here the authors report a 3D structure of the CaMKII holoenzyme in an activation-competent state obtained by single particle EM, and suggest a role for the intrinsically disordered linker domain in facilitating cooperative activation.
- Janette B. Myers
- , Vincent Zaegel
- & Steve L. Reichow
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Article
| Open AccessArchitecture of the RNA polymerase II-Paf1C-TFIIS transcription elongation complex
The Paf1 complex (Paf1C) is an elongation factor assembly that forms the interface between transcribing Pol II and chromatin factors. Here the authors describe the architecture of Paf1C and its interface with Pol II, and show that Paf1C is globally required for normal mRNA transcription in yeast.
- Youwei Xu
- , Carrie Bernecky
- & Patrick Cramer
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Article
| Open AccessLong-range allosteric regulation of the human 26S proteasome by 20S proteasome-targeting cancer drugs
The proteasome regulates several important cellular processes and has been identified as a target for therapeutic interventions. Here the authors map the conformational and energy landscape of the 26S proteasome upon Oprozomib binding and uncover long-range allosteric effects that control the dynamic behaviour of the proteasome.
- David Haselbach
- , Jil Schrader
- & Holger Stark
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Article
| Open AccessStructure of the quaternary complex between SRP, SR, and translocon bound to the translating ribosome
Membrane proteins are inserted co-transnationally through the association between ribosome, the signal recognition particle and its receptor, and the membrane-bound translocon. Here the authors present a cryo-EM reconstruction of this quaternary complex in the activated state and propose a model for signal sequence transfer to the translocon.
- Ahmad Jomaa
- , Yu-Hsien Hwang Fu
- & Nenad Ban
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Article
| Open AccessC. elegans chromosomes connect to centrosomes by anchoring into the spindle network
A connection between centrosomes and chromosomes is a key feature of mitotic spindles. Here the authors generate 3D reconstructions of whole mitotic spindles in earlyC. elegansembryos and show that chromosomes are anchored by the entire spindle network and that connections through kinetochore microtubules are few and likely very transient.
- Stefanie Redemann
- , Johannes Baumgart
- & Thomas Müller-Reichert
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Article
| Open AccessSubnanometre-resolution structure of the doublet microtubule reveals new classes of microtubule-associated proteins
Cilia are hair-like appendages involved in cell motility and sensory reception. Here, the authors report a high resolution cryo-EM structure of the microtubule doublet from motile cilia and identify microtubule inner proteins (MIPs) bound to the inner surface of the doublet that appear to stabilize its structure.
- Muneyoshi Ichikawa
- , Dinan Liu
- & Khanh Huy Bui
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| Open AccessNear-atomic structure of Japanese encephalitis virus reveals critical determinants of virulence and stability
Japanese encephalitis virus (JEV) is a Flavivirus responsible for thousands of deaths every year for which there are no specific anti-virals. Here, Wang et al. report the cryo-EM structure of mature JEV at near-atomic resolution and identify structural elements that modulate stability and virulence.
- Xiangxi Wang
- , Shi-Hua Li
- & Zihe Rao
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| Open AccessCryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains
Host tropism and cell entry of pathogenic coronaviruses are mediated by their envelope spike (S) proteins. Here the authors present structural analyses of trimeric MERS-CoV and SARS-CoV S proteins in pre-fusion conformation, and reveal two states of the receptor binding domain that suggest new avenues for the generation of neutralizing antibodies.
- Yuan Yuan
- , Duanfang Cao
- & George F. Gao
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| Open AccessCell-free reconstitution reveals centriole cartwheel assembly mechanisms
The centriole is an organelle composed of rings of SAS-6 proteins that form a cartwheel structure. Here the authors develop a cell-free system to examine core cartwheel assembly ofC. reinhardtiiproteins and discover that CrSAS-6 has autonomous properties that facilitates self-organized stacking of pairs of rings.
- P. Guichard
- , V. Hamel
- & P. Gönczy
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Article
| Open AccessA human antibody against Zika virus crosslinks the E protein to prevent infection
The human monoclonal antibody ZIKV-117 has demonstrated therapeutic potential against Zika while showing no cross-reactivity to other flaviviruses. Here the authors present a cryo-EM structure of the ZIKV strain H/PF/2013 in complex with the ZIKV-117 Fab, shedding light on its neutralization mechanism.
- S. Saif Hasan
- , Andrew Miller
- & Michael G. Rossmann
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Article
| Open AccessDouble-stranded RNA virus outer shell assembly by bona fide domain-swapping
Double-shelled bacteriophage φ6 is a well-studied model system used to understand assembly of dsRNA viruses. Here the authors report a near-atomic resolution cryo-EM structure of φ6 and propose a model for the structural transitions occurring in the outer shell during genome packaging.
- Zhaoyang Sun
- , Kamel El Omari
- & Juha T. Huiskonen
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Article
| Open AccessStructure and assembly of scalable porous protein cages
Self-assembling proteins that form capsid-like structures act as molecular containers for diverse cargoes. Here, the authors solve the cryo-EM structures of lumazine synthase shells, and show that supercharged mutants form expanded assemblies, indicating that electrostatics can be exploited to engineer cage architecture.
- Eita Sasaki
- , Daniel Böhringer
- & Donald Hilvert
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Article
| Open AccessDissecting the molecular organization of the translocon-associated protein complex
The translocon-associated protein complex (TRAP) is a crucial component of the endoplasmic reticulum protein translocon. Here the authors study native translocon structures from human disease patients and algae cells to determine the molecular organization of the TRAP complex.
- Stefan Pfeffer
- , Johanna Dudek
- & Friedrich Förster
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Article
| Open AccessIdentical folds used for distinct mechanical functions of the bacterial flagellar rod and hook
The bacterial flagellum is a motile organelle that enables bacterial movement. Here the authors explain how the structurally similar flagellum components FlgG and FlgE can give rise to distinct macrostructures—the rod and hook—through subtle differences in domain orientation attributable to a short N-terminal insertion in FlgG.
- Takashi Fujii
- , Takayuki Kato
- & Keiichi Namba
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Article
| Open AccessStructure of actomyosin rigour complex at 5.2 Å resolution and insights into the ATPase cycle mechanism
The cyclic association and dissociation of myosin with actin filament is regulated by ATP binding and hydrolysis cycles. Here the authors report the structure of mammalian skeletal muscle actomyosin rigour complex that provides insights into the ATPase-coupled reaction cycle of actomyosin.
- Takashi Fujii
- & Keiichi Namba
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Article
| Open AccessStructural insights into ribosomal rescue by Dom34 and Hbs1 at near-atomic resolution
mRNA surveillance is essential to maintain homeostasis in eukaryotes and is activated by mRNAs lacking a stop codon. Here the authors describe a high resolution cryo-EM structure of a nonstop complex that shows how arrested ribosome recognition is achieved during Dom34-mediated mRNA surveillance.
- Tarek Hilal
- , Hiroshi Yamamoto
- & Christian M.T. Spahn
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Article
| Open AccessIn vitro protease cleavage and computer simulations reveal the HIV-1 capsid maturation pathway
Two competing models—disassembly/reassembly and displacive—have been proposed for how immature spherical HIV virions transform into mature particles with conical cores. Here the authors provide evidence that both disassembly/reassembly and displacive processes occur sequentially during the maturation process.
- Jiying Ning
- , Gonca Erdemci-Tandogan
- & Peijun Zhang
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Article
| Open AccessAtomic structure of the innexin-6 gap junction channel determined by cryo-EM
Gap junctions have critical roles in maintaining homeostasis in multicellular organisms. Here the authors present cryo-EM structures of the C. elegansinnexin-6 gap junction channel, revealing high structural similarity to human connexin 26 despite a different oligomeric number and lack of sequence similarity.
- Atsunori Oshima
- , Kazutoshi Tani
- & Yoshinori Fujiyoshi
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Article
| Open AccessNeutralization mechanism of a highly potent antibody against Zika virus
There is a pressing need for therapeutic agents against Zika virus (ZIKV). Here the authors present cryoEM structures of a neutralizing antibody (C10) complexed with ZIKV that show C10 preventing structural changes required for virus entry into the cell, suggesting it might be effective in treating Zika infections.
- Shuijun Zhang
- , Victor A. Kostyuchenko
- & Shee-Mei Lok
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Article
| Open AccessStructure of the ribosome post-recycling complex probed by chemical cross-linking and mass spectrometry
Ribosome recycling orchestrated by ABCE1 connects translation termination and mRNA surveillance mechanisms with re-initiation. Using a cross-linking and mass spectrometry approach, Kiosze-Becker et al. provide new information on the large conformational rearrangements that occur during ribosome recycling.
- Kristin Kiosze-Becker
- , Alessandro Ori
- & Robert Tampé
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Article
| Open AccessCryo-EM study of start codon selection during archaeal translation initiation
Initiation factor eIF2, common to eukaryotes and archaea, is a central actor in translation initiation. Here the authors describe two cryo-EM structures of archaeal 30S initiation complexes that provide a novel view of the central role that e/aIF2 plays in start codon selection.
- Pierre-Damien Coureux
- , Christine Lazennec-Schurdevin
- & Yves Mechulam
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Article
| Open AccessComplete structure of the bacterial flagellar hook reveals extensive set of stabilizing interactions
The bacterial flagellar hook is made up of many copies of the protein FlgE. Here, the authors report the full structure of the hook from Campylobacter jejuni and show that its overall structure is different from that of the previously published filament.
- Hideyuki Matsunami
- , Clive S. Barker
- & Fadel A. Samatey
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Article
| Open AccessStructures and stabilization of kinetoplastid-specific split rRNAs revealed by comparing leishmanial and human ribosomes
Leishmania donovani is a protozoan parasite that can cause fatal infections in humans. Here the authors present a high resolution cryoEM structure of the L. donovani80S ribosome and compare it to its human counterpart to provide insight into the basis for drug selectivity towards this eukaryotic parasite.
- Xing Zhang
- , Mason Lai
- & Z. Hong Zhou