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Dimerization and antidepressant recognition at noradrenaline transporter
Cryo-electron microscopy structures of the noradrenaline transporter in the apo state, bound to noradrenaline and bound to various antidepressants shed light on the substrate transport, molecular recognition and dimeric architecture of this protein.
- Heng Zhang
- , Yu-Ling Yin
- & Yi Jiang
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Article |
Plasmid targeting and destruction by the DdmDE bacterial defence system
- Jack P. K. Bravo
- , Delisa A. Ramos
- & David W. Taylor
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Article |
Structural mechanism of angiogenin activation by the ribosome
- Anna B. Loveland
- , Cha San Koh
- & Andrei A. Korostelev
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Article |
Structural pharmacology and therapeutic potential of 5-methoxytryptamines
Detailed analyses of the serotonin receptor 5-HT1A and the psychedelic 5-methoxy-N,N-dimethyltryptamine reveal the differences in receptor structural pharmacology that mediate signalling specificity, efficacy and potency, findings that may facilitate the development of new neuropsychiatric therapeutics.
- Audrey L. Warren
- , David Lankri
- & Daniel Wacker
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Structural basis of lipid head group entry to the Kennedy pathway by FLVCR1
A structural, biochemical and metabolomic analysis reveals the mechanistic basis for transport of extracellular choline and ethanolamine into cells by the human transport protein FLVCR1.
- Yeeun Son
- , Timothy C. Kenny
- & Richard K. Hite
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Structural and molecular basis of choline uptake into the brain by FLVCR2
FLVCR2 is expressed in the blood–brain barrier of mouse and human, and is the major mediator of choline uptake into the brain.
- Rosemary J. Cater
- , Dibyanti Mukherjee
- & Filippo Mancia
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Structures of human γδ T cell receptor–CD3 complex
- Weizhi Xin
- , Bangdong Huang
- & Qiang Zhou
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Article
| Open Access
Mechanism of single-stranded DNA annealing by RAD52–RPA complex
Single-stranded DNA annealing is driven by RAD52 open rings in association with RPA.
- Chih-Chao Liang
- , Luke A. Greenhough
- & Stephen C. West
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Article |
Stepwise activation of a metabotropic glutamate receptor
We propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5, including a series of structures in lipid nanodiscs, from inactive to fully active, with agonist-bound intermediate states.
- Kaavya Krishna Kumar
- , Haoqing Wang
- & Brian K. Kobilka
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Article
| Open Access
Streptomyces umbrella toxin particles block hyphal growth of competing species
Streptomyces are discovered to produce antibacterial protein complexes that selectively inhibit the hyphal growth of related species, a function distinct from that of the small-molecule antibiotics they are known for.
- Qinqin Zhao
- , Savannah Bertolli
- & Joseph D. Mougous
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Promiscuous G-protein activation by the calcium-sensing receptor
Structures of the human calcium-sensing receptor can be bound into complex with G proteins from three different Gα subtypes while maintaining G-protein-binding specificity.
- Hao Zuo
- , Jinseo Park
- & Qing R. Fan
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Article |
Bitter taste receptor activation by cholesterol and an intracellular tastant
Cryo-electron microscopy structures of the type 2 taste receptor TAS2R14 in complex with Ggust and Gi1 identify cholesterol as an orthosteric agonist and the bitter tastant cmpd28.1 as a positive allosteric modulator and agonist.
- Yoojoong Kim
- , Ryan H. Gumpper
- & Bryan L. Roth
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Review Article |
Bridging structural and cell biology with cryo-electron microscopy
The interplay between cryo-electron microscopy and cryo-electron tomography to define complex macromolecular assemblies and visualize them in situ is explored.
- Eva Nogales
- & Julia Mahamid
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Mechanical activation opens a lipid-lined pore in OSCA ion channels
The molecular basis of OSCA/TMEM63 channel mechanosensitivity was investigated by determining 44 cryogenic electron microscopy structures of channels in different environments, expanding understanding of channel-mediated mechanotransduction and pore formation, with implications for two protein families.
- Yaoyao Han
- , Zijing Zhou
- & Yixiao Zhang
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Article
| Open Access
Structural basis of Integrator-dependent RNA polymerase II termination
Cryo-electron microscopy structures of the human Integrator complex in three different functional states shed light on how Integrator terminates RNA polymerase II (Pol II) transcription by disengaging Pol II from the DNA template.
- Isaac Fianu
- , Moritz Ochmann
- & Patrick Cramer
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Article |
Structure and assembly of a bacterial gasdermin pore
Cryo-electron microscopy and molecular dynamics studies of a Vitiosangium gasdermin pore reveal insights into the assembly of this large and diverse family of membrane pore-forming proteins.
- Alex G. Johnson
- , Megan L. Mayer
- & Philip J. Kranzusch
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Article
| Open Access
Cryo-EM structures of RAD51 assembled on nucleosomes containing a DSB site
Cryo-electron microscopy structures of human RAD51 in complex with the nucleosome show that RAD51 can adopt two conformations—rings and filaments—and reveal how RAD51 binds to the nucleosome through its N-terminal lobe domain.
- Takuro Shioi
- , Suguru Hatazawa
- & Hitoshi Kurumizaka
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Article
| Open Access
Blueprinting extendable nanomaterials with standardized protein blocks
A study describes an approach using designed building blocks that are far more regular in geometry than natural proteins to construct modular multicomponent protein assemblies.
- Timothy F. Huddy
- , Yang Hsia
- & David Baker
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Time-resolved cryo-EM of G-protein activation by a GPCR
Time-resolved cryo-EM is used to capture structural transitions during G-protein activation stimulated by a G-protein-coupled receptor.
- Makaía M. Papasergi-Scott
- , Guillermo Pérez-Hernández
- & Georgios Skiniotis
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Article
| Open Access
The molecular basis of sugar detection by an insect taste receptor
A study reports structures of an insect taste receptor in the absence and presence of different sugars, providing details on the molecular basis of sugar detection and selectivity in insects.
- João Victor Gomes
- , Shivinder Singh-Bhagania
- & Joel A. Butterwick
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Article |
Parental histone transfer caught at the replication fork
Structures of the yeast replisome associated with the FACT complex and an evicted histone hexamer offer insights into the mechanism of replication-coupled histone recycling for maintaining epigenetic inheritance.
- Ningning Li
- , Yuan Gao
- & Yuanliang Zhai
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Article
| Open Access
Automated model building and protein identification in cryo-EM maps
ModelAngelo builds atomic models and identifies proteins with unknown sequences in cryo-EM maps.
- Kiarash Jamali
- , Lukas Käll
- & Sjors H. W. Scheres
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Article
| Open Access
Targeted protein degradation via intramolecular bivalent glues
Studies using genetic screening, biophysical characterization and structural reconstitution elucidate the mechanism of action and enable rational design of a new class of functional compounds that glue target proteins to E3 ligases via intramolecularly bridging two domains to enhance intrinsic protein–protein interactions and promote target ubiquitination and degradation.
- Oliver Hsia
- , Matthias Hinterndorfer
- & Alessio Ciulli
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Article |
UFM1 E3 ligase promotes recycling of 60S ribosomal subunits from the ER
Structural and biochemical analyses reveal details of how UFM1 conjugation and deconjugation mediate ribosome recycling and quality control.
- Paul A. DaRosa
- , Ivan Penchev
- & Ron R. Kopito
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Article
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The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER translocons
Attachment of the ubiquitin-like modifier UFM1 to 60S ribosomes has a critical function in the release and recycling of stalled or terminated ribosomes from the endoplasmic reticulum membrane.
- Linda Makhlouf
- , Joshua J. Peter
- & Yogesh Kulathu
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Article
| Open Access
A new family of bacterial ribosome hibernation factors
A study identifies a new bacterial ribosome hibernation factor, Balon, and describes its association with EF-Tu and its initiation of mRNA-independent hibernation during protein synthesis.
- Karla Helena-Bueno
- , Mariia Yu. Rybak
- & Sergey V. Melnikov
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Article |
Structure of human phagocyte NADPH oxidase in the activated state
The cryo-electron microscopy structure of the human phagocyte NADPH oxidase in the activated state provides insight into how cytosolic factors bind to and promote the activating conformational changes of NOX2, facilitating its efficient electron transfer.
- Xiaoyu Liu
- , Yiting Shi
- & Lei Chen
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Article |
Allosteric modulation and G-protein selectivity of the Ca2+-sensing receptor
Cryo-electron microscopy structures of the human calcium-sensing receptor in complex with Gi and Gq proteins reveal how this receptor activates distinct G protein subtypes and how its function is modulated by a variety of ligands.
- Feng He
- , Cheng-Guo Wu
- & Georgios Skiniotis
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Article
| Open Access
Structural basis of ribosomal 30S subunit degradation by RNase R
Cryo-electron microscopy structures of intermediates formed during the degradation of the 30S ribosomal unit shed light on how the 3′ to 5′ exonuclease ribonuclease R controls the ribosomal degradation process.
- Lyudmila Dimitrova-Paternoga
- , Sergo Kasvandik
- & Helge Paternoga
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Article
| Open Access
A new antibiotic traps lipopolysaccharide in its intermembrane transporter
A mechanism of lipid transport inhibition has been identified for a class of peptide antibiotics effective against resistant Acinetobacter strains, which may have applications in the inhibition of other Gram-negative pathogens.
- Karanbir S. Pahil
- , Morgan S. A. Gilman
- & Daniel Kahne
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Oldest thylakoids in fossil cells directly evidence oxygenic photosynthesis
We report the oldest direct evidence of thylakoid membranes in a parallel-to-contorted arrangement within the enigmatic cylindrical microfossils Navifusa majensis from the McDermott Formation, Tawallah Group, Australia (1.78–1.73 Ga).
- Catherine F. Demoulin
- , Yannick J. Lara
- & Emmanuelle J. Javaux
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Article
| Open Access
Structures of the promoter-bound respiratory syncytial virus polymerase
A study reports cryogenic electron microscopy structures of the respiratory syncytial virus polymerase bound to its genomic and antigenomic viral RNA promoters.
- Dongdong Cao
- , Yunrong Gao
- & Bo Liang
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Article
| Open Access
The PfRCR complex bridges malaria parasite and erythrocyte during invasion
Structural studies show how the PfRCR complex of Plasmodium falciparum forms a bridge between erythrocyte and parasite membranes, and how PfCyRPA-binding antibodies neutralize invasion through a steric mechanism, opening the way to new approaches in rational vaccine design.
- Brendan Farrell
- , Nawsad Alam
- & Matthew K. Higgins
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Article
| Open Access
Cryo-EM structures of PP2A:B55–FAM122A and PP2A:B55–ARPP19
Cryo-electron microscopy structures of the PP2A:B55 holoenzyme bound to its inhibitors ARPP19 and FAM122A show distinct binding modes of the two inhibitors.
- Sathish K. R. Padi
- , Margaret R. Vos
- & Wolfgang Peti
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Article
| Open Access
Structures, functions and adaptations of the human LINE-1 ORF2 protein
X-ray crystallography, cryo-electron microscopy, structural modelling, biochemistry, cell biology, and evolutionary analysis enable characterization of ORF2p, the reverse transcriptase of the ancient ‘parasitic’ LINE-1 retrotransposon that has written around one-third of the human genome.
- Eric T. Baldwin
- , Trevor van Eeuwen
- & Martin S. Taylor
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Article
| Open Access
Template and target-site recognition by human LINE-1 in retrotransposition
Human LINE-1 ORF2p relies on upstream single-stranded target DNA to position the adjacent duplex in the endonuclease active site for nicking of the longer DNA strand, with a single nick generating a staggered DNA break.
- Akanksha Thawani
- , Alfredo Jose Florez Ariza
- & Kathleen Collins
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SlyB encapsulates outer membrane proteins in stress-induced lipid nanodomains
SlyB, a lipoprotein in the PhoPQ stress regulon in Gram-negative bacteria, forms stable stress-induced complexes with the outer membrane proteome.
- Arne Janssens
- , Van Son Nguyen
- & Han Remaut
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Transport and inhibition mechanisms of human VMAT2
Structures of human vesicular monoamine transporter 2 in complexes with serotonin and three clinical drugs provide insights into the structural basis for serotonin transport and inhibition of transporter activity by the drugs.
- Di Wu
- , Qihao Chen
- & Daohua Jiang
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Article
| Open Access
TAF15 amyloid filaments in frontotemporal lobar degeneration
Cryogenic electron microscopy structures of amyloid filaments extracted from patient brains reveal that the protein TAF15 forms filaments that characterize certain cases of frontotemporal lobar degeneration.
- Stephan Tetter
- , Diana Arseni
- & Benjamin Ryskeldi-Falcon
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Article
| Open Access
FOXP3 recognizes microsatellites and bridges DNA through multimerization
FOXP3 uses the forkhead domain to form a higher-order multimer after binding to TnG repeat microsatellites.
- Wenxiang Zhang
- , Fangwei Leng
- & Sun Hur
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mRNA reading frame maintenance during eukaryotic ribosome translocation
The accuracy of eukaryotic ribosome translocation relies on eukaryote-specific elements of the 80S ribosome, elongation factor 2 and transfer RNAs, all of which contribute to the maintenance of the messenger RNA reading frame.
- Nemanja Milicevic
- , Lasse Jenner
- & Gulnara Yusupova
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Article
| Open Access
Disease-specific tau filaments assemble via polymorphic intermediates
A time-resolved cryogenic electron microscopy analysis provides structural information on the processes of primary and secondary nucleation of tau amyloid formation, with implications for the development of new therapies.
- Sofia Lövestam
- , David Li
- & Sjors H. W. Scheres
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Article
| Open Access
HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes
HIV-1 Env trimers bound to one, two and three CD4 molecules are observed at membrane–membrane interfaces between HIV-1 and CD4-decorated virus-like particles.
- Wenwei Li
- , Zhuan Qin
- & Walther Mothes
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Article
| Open Access
Intermediate conformations of CD4-bound HIV-1 Env heterotrimers
Single-particle cryo-electron microscopy structures of HIV-1 envelope (Env) trimers bound to one or two CD4 receptors identify intermediate Env conformations that precede host–virus fusion and inform the design of therapeutics to prevent HIV-1 infection.
- Kim-Marie A. Dam
- , Chengcheng Fan
- & Pamela J. Bjorkman
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Recognition of methamphetamine and other amines by trace amine receptor TAAR1
We report on the structures of the TAAR1–G-protein complex when bound to methamphetamine and other amines.
- Heng Liu
- , You Zheng
- & Fei Xu
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Ligand recognition and G-protein coupling of trace amine receptor TAAR1
TAAR1 has a rigid consensus binding motif that binds to endogenous trace amine stimuli as well as two extended binding pockets that accommodate diverse chemotypes.
- Zheng Xu
- , Lulu Guo
- & Zhenhua Shao
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Mechanisms of neurotransmitter transport and drug inhibition in human VMAT2
Structures of a vesicular monoamine transporter in complex with drugs and substrate provide insights into the physiology and pharmacology of neurotransmitter packaging.
- Shabareesh Pidathala
- , Shuyun Liao
- & Chia-Hsueh Lee
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Article
| Open Access
Structure of the native myosin filament in the relaxed cardiac sarcomere
A cryo-electron tomography study reports the structure of thick myosin filaments of mouse cardiac muscle in the relaxed state in situ and the MyBP-C links that connect them with the surrounding thin actin filaments.
- Davide Tamborrini
- , Zhexin Wang
- & Stefan Raunser
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Cryo-EM structure of the human cardiac myosin filament
The intricate molecular architecture and interactions of the human cardiac myosin filament offer insights into cardiac physiology, disease and drug therapy.
- Debabrata Dutta
- , Vu Nguyen
- & Roger Craig
Physiological temperature drives TRPM4 ligand recognition and gating