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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
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Article
| Open AccessA 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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Research Briefing |
High-resolution structures of two phosphatase–inhibitor complexes
Progression into the final phase of the cell cycle is driven mainly by protein phosphorylation, although it also requires the inhibition of phosphatase proteins, such as the PP2A:B55 complex. The structures reveal how PP2A:B55 binds to two of its inhibitors.
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| Open AccessStructures 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 AccessThe 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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| Open AccessCryo-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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News & Views |
How brine shrimps cope with salt
Mutant ion pumps help brine shrimp survive highly saline waters.
- Lucia Brunello
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Article
| Open AccessStructures, 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 AccessTemplate 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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News & Views |
Structures of the amphetamine-binding receptor will aid drug discovery
High-resolution structures of TAAR1 — the receptor bound by amphetamines and molecules called trace amines — reveal detailed interactions with ligand molecules that will inform efforts to design antipsychotic drugs.
- Harald H. Sitte
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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 AccessTAF15 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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Research Briefing |
Atomic-level structures show how accuracy is maintained in protein synthesis
A series of structures of the eukaryotic protein-synthesis machinery are imaged at high resolution in defined states of the elongation phase of protein synthesis. Analysis suggests that there are underlying molecular mechanisms that increase the accuracy of translation of genetic information in eukaryotes.
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News & Views |
An immune-cell transcription factor tethers DNA together
A transcription factor in immune cells forms an unexpectedly ladder-like complex with two DNA molecules, allowing the expression of genes that these cells need to suppress harmful immune responses.
- Zhi Liu
- & Ye Zheng
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Article
| Open AccessFOXP3 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 AccessDisease-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 AccessHIV-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 AccessStructural insights into intron catalysis and dynamics during splicing
Analysis of the group II intron ribonucleoprotein shows the molecular interactions involved in branchpoint adenosine recognition, lariat formation and exon ligation, providing clues to the evolutionary conservation of structural components and catalytic mechanisms in premessenger RNA splicing.
- Ling Xu
- , Tianshuo Liu
- & Anna Marie Pyle
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Article
| Open AccessStructural basis of Gabija anti-phage defence and viral immune evasion
X-ray crystallography, cryo-EM and biochemical analysis provide insight into the assembly of the bacterial Gabija complex, an anti-phage system, and reveal how viruses can evade this defence mechanism.
- Sadie P. Antine
- , Alex G. Johnson
- & Philip J. Kranzusch
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Recognition and maturation of IL-18 by caspase-4 noncanonical inflammasome
Activated human caspase-4 directly and efficiently processes IL-18 in vitro and during bacterial infections, cleaving the same tetrapeptide site in pro-IL-18 as caspase-1.
- Xuyan Shi
- , Qichao Sun
- & Feng Shao
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Article
| Open AccessIntermediate 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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| Open AccessThe social and structural architecture of the yeast protein interactome
A protein interaction network constructed with data from high-throughput affinity enrichment coupled to mass spectrometry provides a highly saturated yeast interactome with 31,004 interactions, including low-abundance complexes, membrane protein complexes and non-taggable protein complexes.
- André C. Michaelis
- , Andreas-David Brunner
- & Matthias Mann
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| Open AccessPredicting multiple conformations via sequence clustering and AlphaFold2
An analysis of the evolutionary distribution of predicted structures for the metamorphic protein KaiB using AF-Cluster reveals that both conformations of KaiB were distributed in clusters across the KaiB family.
- Hannah K. Wayment-Steele
- , Adedolapo Ojoawo
- & Dorothee Kern
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Article |
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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News & Views |
Getting to the heart of thick-filament structure
Thick filaments contain the protein myosin that generates the force of every heartbeat. Two studies report how these myosin molecules pack together in thick filaments with other proteins to form a surprisingly complex structure.
- Peter J. Knight
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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 AccessStructure 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
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News & Views |
An ion transporter in sperm that has features of a channel
A membrane-transport protein in sperm exchanges sodium and hydrogen ions. Its activations by voltage and by cyclic nucleotide molecules are usually only features of ion channels. Structural data shed light on this protein.
- John Orlowski
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| Open AccessStructure and electromechanical coupling of a voltage-gated Na+/H+ exchanger
Upon hyperpolarization, the S4 voltage-sensing segment of sea urchin SLC9C1 moves down, removing inhibition caused by an intracellular helix and enabling Na+/H+ exchange, leading to pH-dependent activation of sAC and sperm chemotaxis.
- Hyunku Yeo
- , Ved Mehta
- & David Drew
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| Open AccessStructures of a sperm-specific solute carrier gated by voltage and cAMP
This study proposes a molecular mechanism of voltage activation in SLC9C1, a transporter essential for male fertility.
- Valeria Kalienkova
- , Martin F. Peter
- & Cristina Paulino
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Technology Feature |
Soft-landing methods aim to simplify structural biology
Linking mass spectrometry with cryo-electron microscopy could transform understanding of complex protein structures — if scientists can show that samples remain intact when they hit their target.
- Michael Eisenstein
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News |
How AlphaFold and other AI tools could help us prepare for the next pandemic
Researchers are using machine-learning programs to predict the evolution of viruses and design vaccines.
- Ewen Callaway
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Article
| Open AccessStructures illustrate step-by-step mitochondrial transcription initiation
A cryogenic electron microscopy study presents structures characterizing the initiation of RNA synthesis by yeast mitochondrial RNA polymerase at single-nucleotide addition steps.
- Quinten Goovaerts
- , Jiayu Shen
- & Kalyan Das
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| Open AccessSialoglycan binding triggers spike opening in a human coronavirus
Binding of a sialoglycan-based primary receptor by the spike protein of the common cold human coronavirus HKU1 triggers conformational changes to a state that would allow binding to a second receptor required for cell entry.
- Matti F. Pronker
- , Robert Creutznacher
- & Daniel L. Hurdiss
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Nucleic-acid-triggered NADase activation of a short prokaryotic Argonaute
Cryo-electron microscopy structures of a short prokaryotic Argonaute (pAgo) and the associated TIR-APAZ proteins bound by guide RNA and target DNA shed light on the mechanisms of assembly and activation of pAgo systems.
- Xiaopan Gao
- , Kun Shang
- & Sheng Cui
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Review Article |
Molecular pathology of neurodegenerative diseases by cryo-EM of amyloids
Structural studies of amyloid filaments purified from brains of people with neurodegenerative diseases link specific amyloid folds with distinct diseases and provide a basis for the development of models of neurodegenerative disease.
- Sjors H. W. Scheres
- , Benjamin Ryskeldi-Falcon
- & Michel Goedert
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| Open AccessInactivation of the Kv2.1 channel through electromechanical coupling
The exploration of voltage-gated potassium channels using cryo-electron microscopy and electrophysiology identifies a mechanism of inactivation involved in regulating neuron firing.
- Ana I. Fernández-Mariño
- , Xiao-Feng Tan
- & Kenton J. Swartz
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| Open AccesspiRNA processing by a trimeric Schlafen-domain nuclease
The endoribonuclease PUCH, a trimer of Schlafen-like-domain proteins, initiates piRNA processing in the nematode Caenorhabditis elegans through 5′-end piRNA precursor cleavage.
- Nadezda Podvalnaya
- , Alfred W. Bronkhorst
- & René F. Ketting
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News |
AlphaFold touted as next big thing for drug discovery — but is it?
Questions remain about whether the AI tool for predicting protein structures can really shake up the pharmaceutical industry.
- Carrie Arnold
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Article
| Open AccessCryo-EM structures reveal native GABAA receptor assemblies and pharmacology
Using cryo-EM, structures of three major assemblies of type A GABA receptors, which regulate brain excitability, are revealed in the mouse brain and provide a basis for the development of subtype-specific drugs.
- Chang Sun
- , Hongtao Zhu
- & Eric Gouaux
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Technology Feature |
Catching proteins at play: the method revealing the cell’s inner mysteries
Cryo-electron tomography is a hugely promising tool in visual proteomics — if researchers can work out what they are seeing.
- Michael Eisenstein