Featured
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Research Briefing |
A chemical method for selective labelling of the key amino acid tryptophan
A broadly applicable method allows selective, rapid and efficient chemical modification of the side chain of tryptophan amino acids in proteins. This platform enables systematic, proteome-wide identification of tryptophan residues, which can form a bond (called cation–π interaction) with positively charged molecules. Such interactions are key in many biochemical processes, including protein-mediated phase separation.
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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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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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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 |
Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids
Glucocorticoids reprogram the mitochondrial metabolism of macrophages, resulting in increased and sustained production of the anti-inflammatory metabolite itaconate and, as a consequence, inhibition of the inflammatory response.
- Jean-Philippe Auger
- , Max Zimmermann
- & Gerhard Krönke
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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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Article
| Open AccessMolecular insights into capsular polysaccharide secretion
An ensemble of cryo-electron microscopy structures of the KpsMT ABC transporter in complex with the KpsE co-polymerase and a glycolipid substrate reveal how capsular polysaccharides are recognized and translocated across bacterial cell membranes.
- Jeremi Kuklewicz
- & Jochen Zimmer
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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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Where I Work |
I study small organisms to tackle big climate problems
Marine biologist Gabriel Renato Castro cultivates compounds from cyanobacteria to support agriculture and the environment.
- Nikki Forrester
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Article |
Structural insights into vesicular monoamine storage and drug interactions
Monoamines and neurotoxicants share a binding pocket in VMAT1 featuring polar sites for specificity and a wrist-and-fist shape for versatility, and monoamine enrichment in storage vesicles arises from dominant import via favoured lumenal-open transition of VMAT1 and protonation-precluded binding during its cytoplasmic-open transition.
- Jin Ye
- , Huaping Chen
- & Weikai Li
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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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Article
| Open AccessSubstrate-induced condensation activates plant TIR domain proteins
Binding of the substrates NAD+ and ATP to the plant Toll/interleukin-1 receptor (TIR) domain proteins induces phase separation and, thereby, activation of TIR enzymatic and immune signalling activity.
- Wen Song
- , Li Liu
- & Jijie Chai
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Research Briefing |
Dysregulated cellular stress management becomes a source of stress
Stress responses protect cells from harmful conditions, but once the stress has resolved, these responses must be actively turned off to avoid cell damage that might lead to the development of neurodegenerative disease.
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Matters Arising |
Model uncertainty obscures major driver of soil carbon
- Xianjin He
- , Rose Z. Abramoff
- & Daniel S. Goll
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Review Article |
Ion and lipid orchestration of secondary active transport
This Review describes the various mechanisms of ion-coupled transport across membranes and how the activities of transporter proteins are modulated by the composition of the lipid bilayer.
- David Drew
- & Olga Boudker
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Article
| Open AccessThe CRL5–SPSB3 ubiquitin ligase targets nuclear cGAS for degradation
The ubiquitin proteasomal system degrades nuclear cGAS in cycling cells.
- Pengbiao Xu
- , Ying Liu
- & Andrea Ablasser
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Article |
CST–polymerase α-primase solves a second telomere end-replication problem
Incomplete duplication of the C-rich telomeric repeat strand by lagging-strand DNA synthesis is counteracted by DNA synthesis mediated by CST–polymerase α-primase.
- Hiroyuki Takai
- , Valentina Aria
- & Titia de Lange
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Technology Feature |
How phase separation is revolutionizing biology
Imaging and molecular manipulation reveal how biomolecular condensates form and offer clues to the role of phase separation in health and disease.
- Elie Dolgin
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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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Article
| Open AccessIL-10 constrains sphingolipid metabolism to limit inflammation
IL-10 exerts its anti-inflammatory activity in macrophages by increasing the expression of enzymes that promote fatty acid desaturation and downstream regulation of the transcription factor REL.
- Autumn G. York
- , Mathias H. Skadow
- & Richard A. Flavell
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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 |
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 AccessBile salt hydrolase catalyses formation of amine-conjugated bile acids
We find that bile salt hydrolase N-acyltransferase activity can form bacterial bile acid amidates that are positively correlated with the colonization of gut bacteria that assist in the regulation of the bile acid metabolic network.
- Bipin Rimal
- , Stephanie L. Collins
- & Andrew D. Patterson
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Article |
Bile salt hydrolase acyltransferase activity expands bile acid diversity
Acyltransferase activity of the enzyme bile salt hydrolase is identified and shown to mediate microbial bile acid conjugation, diversifying the bile acid pool and expanding their role in gut physiology.
- Douglas V. Guzior
- , Maxwell Okros
- & Robert A. Quinn
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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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Article |
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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Article
| Open AccessStress response silencing by an E3 ligase mutated in neurodegeneration
The E3 ligase SIFI is identified as a dedicated silencing factor of the integrated stress response, a finding that has implications for the development of therapeutics for neurodegenerative diseases caused by mitochondrial protein import stress.
- Diane L. Haakonsen
- , Michael Heider
- & Michael Rapé
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Article |
Coordination of cohesin and DNA replication observed with purified proteins
We study the interplay between cohesin and replication by reconstituting a functional replisome using purified proteins, showing how cohesin initially responds to replication and providing a molecular model for the establishment of sister chromatid cohesion.
- Yasuto Murayama
- , Shizuko Endo
- & Hiroyuki Araki
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Article
| Open AccessThe HIV capsid mimics karyopherin engagement of FG-nucleoporins
Dissection of the nuclear pore complex provides a model in which the HIV capsid enters the nucleus through karyopherin mimicry, a mechanism likely to be conserved across other viruses.
- C. F. Dickson
- , S. Hertel
- & D. A. Jacques
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Article
| Open AccessAlternative splicing of latrophilin-3 controls synapse formation
Latrophilin-3 organizes synapses through a convergent dual-pathway mechanism in which Gαs signalling is activated and phase-separated postsynaptic protein scaffolds are recruited.
- Shuai Wang
- , Chelsea DeLeon
- & Thomas C. Südhof
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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 AccessMRE11 liberates cGAS from nucleosome sequestration during tumorigenesis
The double-strand break sensor MRE11 is identified as a pivotal mediator of cGAS activation in response to multiple types of DNA damage.
- Min-Guk Cho
- , Rashmi J. Kumar
- & Gaorav P. Gupta
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Article
| 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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Research Briefing |
Oceans can capture more carbon dioxide than previously thought
The strength of the biological carbon pump was estimated using direct measurements of nutrients collected over decades. The findings indicate that ocean waters can capture and store larger amounts of carbon dioxide than previously estimated. This might have implications for climate-change models.
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Article |
A light-driven enzymatic enantioselective radical acylation
Enzyme-bound ketyl radicals derived from thiamine diphosphate are selectively generated through single-electron oxidation by a photoexcited organic dye and shown to lead to enantioselective radical acylation reactions.
- Yuanyuan Xu
- , Hongwei Chen
- & Xiaoqiang Huang
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Article
| Open AccessDe novo design of high-affinity binders of bioactive helical peptides
A study describes a direct computational approach without experimental optimization to design high-affinity proteins that bind small helical peptides.
- Susana Vázquez Torres
- , Philip J. Y. Leung
- & David Baker
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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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Article |
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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Article |
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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News |
Are your organs ageing well? The blood holds clues
One organ in a person’s body can age faster than the rest — with implications for health and mortality.
- Max Kozlov
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Article
| Open AccessReverse metabolomics for the discovery of chemical structures from humans
A new discovery strategy, ‘reverse metabolomics’, facilitates high-throughput matching of mass spectrometry spectra in public untargeted metabolomics datasets, and a proof-of-concept experiment identified an association between microbial bile amidates and inflammatory bowel disease.
- Emily C. Gentry
- , Stephanie L. Collins
- & Pieter C. Dorrestein
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Research Highlight |
A low-cost electron microscope maps proteins at speed
Bespoke cryo-electron microscope reveals 3D details of cellular structures — and is an order of magnitude cheaper than its rivals.
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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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Article |
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 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 |
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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