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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 |
Accurate structure prediction of biomolecular interactions with AlphaFold 3
- Josh Abramson
- , Jonas Adler
- & John M. Jumper
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Research Briefing |
Toad psychedelic points to biological target for antidepressants
A hallucinogenic compound secreted by toads has served as a springboard for research into the therapeutic benefits of psychedelics. The findings suggest that these compounds exert antidepressant effects in part by binding an under-appreciated target in the brain.
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News |
Major AlphaFold upgrade offers boost for drug discovery
Latest version of the AI models how proteins interact with other molecules — but DeepMind restricts access to the tool.
- Ewen Callaway
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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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Article
| Open AccessDiscovery of potent small-molecule inhibitors of lipoprotein(a) formation
Biochemical screening and optimization identify small molecules that inhibit the formation of lipoprotein(a), and these inhibitors reduce the levels of Lp(a) in several animal models, suggesting that they could provide a therapeutic option in humans.
- Nuria Diaz
- , Carlos Perez
- & Laura F. Michael
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Article |
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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Article |
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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Article |
Structures of human γδ T cell receptor–CD3 complex
- Weizhi Xin
- , Bangdong Huang
- & Qiang Zhou
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Article
| Open AccessMechanism 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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News & Views |
Charles Darwin investigates: the curious case of primrose punishment
Birds emerge as top suspects for unexplained flower mutilation, and reflections from 1974 mark the 21st anniversary of the discovery of the DNA double helix, in the weekly dip into Nature’s archive.
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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 AccessStreptomyces 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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Article |
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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News & Views |
A step along the path towards AlphaFold — 50 years ago
Paring down the astronomical complexity of the protein-folding problem, plus Isaac Newton’s ambiguous use of the word ‘axiom’, in the weekly dip into Nature’s archive.
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News & Views |
A bitter taste receptor activated in a surprising way
The sensing of bitter taste results from the complex interplay of many chemical cues and a range of receptors. It emerges that this complexity might be built-in even at the level of individual receptors.
- Antonella Di Pizio
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Article
| Open AccessEmergence of fractal geometries in the evolution of a metabolic enzyme
Citrate synthase from the cyanobacterium Synechococcus elongatus is shown to self-assemble into Sierpiński triangles, a finding that opens up the possibility that other naturally occurring molecular-scale fractals exist.
- Franziska L. Sendker
- , Yat Kei Lo
- & Georg K. A. Hochberg
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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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Article |
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 AccessStructural 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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Nature Podcast |
How climate change is affecting global timekeeping
Melting polar ice could delay major time adjustment, and the strange connection between brain inflammation and memory.
- Elizabeth Gibney
- & Nick Petrić Howe
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Article |
Structural basis of exoribonuclease-mediated mRNA transcription termination
A study presents two cryo-EM structures of yeast Pol II pre-termination transcription complexes bound to Rat1–Rai1, and provides the mechanisms for termination of mRNA transcription in yeast and other eukaryotes.
- Yuan Zeng
- , Hong-Wei Zhang
- & Yu Zhang
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News Feature |
These ‘movies’ of proteins in action are revealing the hidden biology of cells
A burgeoning technique called time-resolved cryo-EM is granting insights into the tiny motors and devices that power life.
- Ewen Callaway
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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 AccessCryo-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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News |
‘A landmark moment’: scientists use AI to design antibodies from scratch
Modified protein-design tool could make it easier to tackle challenging drug targets — but AI antibodies are still a long way from reaching the clinic.
- Ewen Callaway
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Article
| Open AccessBlueprinting 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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Article |
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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News |
Could AI-designed proteins be weaponized? Scientists lay out safety guidelines
AI tools that can come up with protein structures at the push of a button should be used safely and ethically, say researchers in the field.
- Ewen Callaway
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Article
| Open AccessThe 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 AccessAutomated 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 AccessTargeted 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 |
Activation of Thoeris antiviral system via SIR2 effector filament assembly
A study reports that the Theoris anti-phage defence system is activated through helical filament assembly of the ThsA effector and details the activation mechanism.
- Giedre Tamulaitiene
- , Dziugas Sabonis
- & Virginijus Siksnys
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Article
| Open AccessThe 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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News & Views Forum |
Energetic laser pulses alter outcomes of X-ray studies of proteins
Cutting-edge X-ray sources have enabled the structural dynamics of proteins to be tracked during biochemical processes, but the findings have been questioned. Two experts discuss the implications of a study that digs into this issue.
- Richard Neutze
- & R. J. Dwayne Miller
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Article
| Open AccessA 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
| Open AccessInfluence of pump laser fluence on ultrafast myoglobin structural dynamics
Ultrafast time-resolved serial femtosecond crystallography is used to investigate a photodissociation reaction in a protein, revealing the strong impact of the pump laser fluence on the structural changes and the reaction mechanism.
- Thomas R. M. Barends
- , Alexander Gorel
- & Ilme Schlichting
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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 AccessStructural 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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Conformational ensembles of the human intrinsically disordered proteome
A computational model generates conformational ensembles of 28,058 intrinsically disordered proteins and regions (IDRs) in the human proteome and sheds light on the relationship between sequence, conformational properties and functions of IDRs.
- Giulio Tesei
- , Anna Ida Trolle
- & Kresten Lindorff-Larsen
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Technology Feature |
Seven technologies to watch in 2024
Advances in artificial intelligence are at the heart of many of this year’s most exciting areas of technological innovation
- Michael Eisenstein
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News & Views |
Snapshots of genetic copy-and-paste machinery in action
LINE-1 DNA elements self-duplicate, inserting the copy into new regions of the genome — a key process in chromosome evolution. Structures of the machinery that performs this process in humans are now reported.
- Gael Cristofari
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Article
| Open AccessThe CRISPR effector Cam1 mediates membrane depolarization for phage defence
The prokaryotic non-enzymatic effector protein Cam1 mediates CRISPR immunity by binding tetra-adenylate second messengers and forming a pore in the membrane that induces membrane depolarization and growth arrest.
- Christian F. Baca
- , You Yu
- & Luciano A. Marraffini