Featured
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Article
| Open Access
Genome expansion by a CRISPR trimmer-integrase
CRISPR systems lacking Cas4 can use fused or recruited exonucleases for faithful acquisition of new CRISPR immune sequences.
- Joy Y. Wang
- , Owen T. Tuck
- & Jennifer A. Doudna
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News & Views |
Infancy of sterol biosynthesis hints at extinct eukaryotic species
A newly discovered fossil record of steroid molecules, spanning 1.64 billion years, points to ancient organisms in the eukaryotic domain being capable of only early steps in the synthesis of sterol molecules.
- Fabien Kenig
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News |
A ‘lost world’ of early microbes thrived one billion years ago
Fat-like compounds in ancient rocks point to a vast array of previously unknown microorganisms that once dominated complex life on Earth.
- Heidi Ledford
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Article
| Open Access
Structural basis for FGF hormone signalling
This study reveals how Klotho and heparan sulfate glycosaminoglycan coreceptors enable FGF hormones to induce asymmetric 1:2 FGF–FGFR dimerization mandatory for FGFR kinase activation and hence signalling.
- Lingfeng Chen
- , Lili Fu
- & Moosa Mohammadi
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Article |
Cryo-EM structure of SARS-CoV-2 postfusion spike in membrane
The SARS-CoV-2 spike internal fusion peptide forms a hairpin-like wedge that spans almost the entire lipid bilayer and the transmembrane segment wraps around the fusion peptide at the last stage of membrane fusion.
- Wei Shi
- , Yongfei Cai
- & Bing Chen
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Article |
Outer membrane utilisomes mediate glycan uptake in gut Bacteroidetes
A structural and functional analysis of the systems involved in oligosaccharide uptake in gut Bacteroidetes describes multicomponent complexes termed utilisomes that include pre-processing and transport subunits.
- Joshua B. R. White
- , Augustinas Silale
- & Neil A. Ranson
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Article
| Open Access
A cytosolic surveillance mechanism activates the mitochondrial UPR
We identify a highly controlled cytosolic surveillance mechanism that integrates independent mitochondrial stress signals to initiate the mitochondrial unfolded protein response (UPR), revealing a link between mitochondrial and cytosolic proteostasis.
- F. X. Reymond Sutandy
- , Ines Gößner
- & Christian Münch
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News & Views |
How a protein differentiates between rare-earth elements
A protein has been discovered that binds to the lighter members of the rare-earth family of metals more strongly than to the heavier ones — an amazing feat, given the chemical similarities of these elements.
- Scott Banta
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Article
| Open Access
Enhanced rare-earth separation with a metal-sensitive lanmodulin dimer
A study biochemically and structurally characterizes a lanmodulin from Hansschlegelia quercus with an oligomeric state sensitive to rare-earth ionic radius.
- Joseph A. Mattocks
- , Jonathan J. Jung
- & Joseph A. Cotruvo Jr
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Research Highlight |
How to lock away more carbon: give mangroves a little love
Restored mangroves and seagrass meadows could suck more carbon from the atmosphere.
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Outlook |
Disrupting protein folding to tackle cancer
Intermediate states show promise as drug targets.
- Elie Dolgin
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Article |
Structural basis of amine odorant perception by a mammal olfactory receptor
Cryo-electron microscopy structures of mouse trace amine-associated receptor 9 reveals structural motifs involved in odorant ligand recognition, including a unique disulfide bond linking the N terminus to extracellular loop 2.
- Lulu Guo
- , Jie Cheng
- & Jin-Peng Sun
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Article
| Open Access
Ångström-resolution fluorescence microscopy
The authors introduce a single-molecule DNA-barcoding method, resolution enhancement by sequential imaging, that improves the resolution of fluorescence microscopy down to the Ångström scale using off-the-shelf fluorescence microscopy hardware and reagents.
- Susanne C. M. Reinhardt
- , Luciano A. Masullo
- & Ralf Jungmann
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Article
| Open Access
Programming inactive RNA-binding small molecules into bioactive degraders
Small-molecule RNA-targeted degradation can be leveraged to convert strong, yet inactive, binding interactions into potent and specific modulators of RNA function.
- Yuquan Tong
- , Yeongju Lee
- & Matthew D. Disney
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Article |
A small-molecule PI3Kα activator for cardioprotection and neuroregeneration
A new specific, small-molecule activator of the PI3Kα isoform (UCL-TRO-1938) identified through high-throughput screening can transiently activate PI3K signalling and biological responses in cells and tissues, with potential therapeutic applications in tissue protection and regeneration.
- Grace Q. Gong
- , Benoit Bilanges
- & Bart Vanhaesebroeck
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News & Views |
The role of NINJ1 protein in programmed cellular destruction
The protein NINJ1 drives membrane rupture associated with certain types of cell death. Investigation of NINJ1 reveals mechanistic details of how it functions, raising the possibility of developing new therapeutics.
- James C. Whisstock
- & Ruby H. P. Law
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Article |
RNA conformational propensities determine cellular activity
Systematic alteration of HIV-1 TAR RNA and quantitative determination of its propensity to bind to the Tat protein establish a key role role for a rare and short-lived RNA state in Tat-dependent transactivation in cells.
- Megan L. Ken
- , Rohit Roy
- & Hashim M. Al-Hashimi
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Article
| Open Access
Structural basis of NINJ1-mediated plasma membrane rupture in cell death
Structural, biochemical and mutagenesis studies indicate that, in dying cells, the membrane protein NINJ1 assembles into filaments, disrupting the cell membrane.
- Morris Degen
- , José Carlos Santos
- & Sebastian Hiller
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Article
| Open Access
Uridine-derived ribose fuels glucose-restricted pancreatic cancer
A metabolite screen of pancreatic cells shows that pancreatic cancer cells metabolize uridine-derived ribose via UPP1, supporting redox balance, survival and proliferation.
- Zeribe C. Nwosu
- , Matthew H. Ward
- & Costas A. Lyssiotis
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News |
Deadly mushroom poison might now have an antidote — with help from CRISPR
Gene-editing technique might have finally cracked the mystery of how death cap mushrooms kill.
- Saima Sidik
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News & Views |
A clue to the catalytic activation of splicing
The processing of messenger RNA during splicing requires the activity of a complex of RNAs and proteins termed the spliceosome. Structural data shed light on previously mysterious aspects of splicing in humans.
- Soo-Chen Cheng
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Article |
Testosterone histories from tusks reveal woolly mammoth musth episodes
Comparisons of steroid hormone concentrations in dentin samples from fossil mammoth tusks with those from a modern elephant tusk provide evidence of periodic increases in testosterone in the male mammoth characteristic of musth episodes.
- Michael D. Cherney
- , Daniel C. Fisher
- & Alexei N. Tikhonov
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Article
| Open Access
The electron–proton bottleneck of photosynthetic oxygen evolution
Microsecond infrared spectroscopy together with quantum chemistry reveal the rate-determining proton and electron movements and identify an oxygen-radical state of the manganese cluster as the S4 state.
- Paul Greife
- , Matthias Schönborn
- & Holger Dau
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Article |
Complete integration of carbene-transfer chemistry into biosynthesis
The α-diazoester azaserine can be produced by Streptomyces albus engineered with a biosynthetic gene cluster and act as the carbene precursor for coupling with intracellularly produced styrene to generate unnatural amino acids containing a cyclopropyl group.
- Jing Huang
- , Andrew Quest
- & Jay D. Keasling
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Article |
Structural basis of BAM-mediated outer membrane β-barrel protein assembly
The structural basis of the late-stage intermediate assembly of outer membrane β-barrel proteins mediated by the bacterial β-barrel assembly machinery is determined.
- Chongrong Shen
- , Shenghai Chang
- & Haohao Dong
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Editorial |
How Rosalind Franklin was let down by DNA’s dysfunctional team
The story of how the structure of DNA was found is one of team science from which one member was unforgivably excluded.
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Comment |
What Rosalind Franklin truly contributed to the discovery of DNA’s structure
Franklin was no victim in how the DNA double helix was solved. An overlooked letter and an unpublished news article, both written in 1953, reveal that she was an equal player.
- Matthew Cobb
- & Nathaniel Comfort
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Article |
Lesion recognition by XPC, TFIIH and XPA in DNA excision repair
Cryo-electron microscopy structures reveal how XPC recognizes DNA lesions and recruits XPA and the TFIIH core complex for lesion verification in nucleotide excision repair.
- Jinseok Kim
- , Chia-Lung Li
- & Wei Yang
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Article
| Open Access
CTCF is a DNA-tension-dependent barrier to cohesin-mediated loop extrusion
CTCF is sufficient to block loop extruding cohesin in a DNA tension dependent manner, and induces loop extrusion direction switching and loop shrinkage.
- Iain F. Davidson
- , Roman Barth
- & Jan-Michael Peters
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Article |
Noncoding translation mitigation
Combining genome-wide CRISPR screens with massively parallel analyses of human and random DNA sequences reveal a unified mechanism for the surveillance and evolution of translation products from annotated noncoding DNA.
- Jordan S. Kesner
- , Ziheng Chen
- & Xuebing Wu
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Article |
mRNA recognition and packaging by the human transcription–export complex
Cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNA ribonucleoprotein complexes bound to the transcription–export complex reveal how mRNAs are packaged and recognized for nuclear export.
- Belén Pacheco-Fiallos
- , Matthias K. Vorländer
- & Clemens Plaschka
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Article
| Open Access
De novo design of modular peptide-binding proteins by superhelical matching
A computational approach is used to design modular proteins that bind to synthetic peptides and disordered regions of human proteins with high affinity and specificity.
- Kejia Wu
- , Hua Bai
- & David Baker
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Article |
Establishment and function of chromatin organization at replication origins
Genome-scale in vitro reconstitution of DNA replication through chromatin establishes a crucial role for the origin recognition complex in organizing nucleosome arrays that are crucial for the initiation of replication.
- Erika Chacin
- , Karl-Uwe Reusswig
- & Christoph F. Kurat
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Article
| Open Access
Cryo-EM structure of the transposon-associated TnpB enzyme
Cryo-electron microscopy analysis of the Deinococcus radiodurans ISDra2 TnpB in complex with its cognate ωRNA and target DNA provides insights into the mechanism of TnpB function and the evolution of CRISPR–Cas12 effectors.
- Ryoya Nakagawa
- , Hisato Hirano
- & Osamu Nureki
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Article |
TnpB structure reveals minimal functional core of Cas12 nuclease family
Cryo-EM structures of D. radiodurans TnpB–reRNA complex in DNA-bound and -free forms reveal the basic architecture of TnpB nuclease and the molecular mechanism for DNA target recognition and cleavage supported by biochemical experiments.
- Giedrius Sasnauskas
- , Giedre Tamulaitiene
- & Virginijus Siksnys
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Research Highlight |
Algal enzyme fed just the right diet churns out green fuel
An enzyme rapidly makes hydrocarbons found in petrol if it has the right fatty acid as a reagent.
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Research Briefing |
Genome-based scores predict thousands of molecular traits in humans
Genetic scores for predicting levels of several types of biomolecule have been developed and validated in people of diverse ancestries, and used to uncover insights into disease biology. An open resource to disseminate these scores, OmicsPred, will enable researchers to predict various molecular traits from genetic profiles in their own data sets.
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Article |
Structural mechanisms for regulation of GSDMB pore-forming activity
The cryo-EM structure of the GSDMB pore reveals mechanisms by which GSDMB pore-forming activity is regulated by pathogenic bacteria and mRNA splicing.
- Xiu Zhong
- , Huan Zeng
- & Jingjin Ding
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News & Views |
Earliest molecular events of vision revealed
Light-sensitive proteins called rhodopsins in the vertebrate eye initiate the cellular processes of vision. Leading-edge crystallography experiments have revealed the molecular mechanism by which light activates these proteins.
- Marius Schmidt
- & Emina A. Stojković
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News |
Fruit flies are first known animals that can taste alkaline foods
The ability to detect high pH could allow the insects to avoid toxic substances.
- Smriti Mallapaty
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Article
| Open Access
From primordial clocks to circadian oscillators
X-ray, cryo-EM and kinetic studies of the circadian oscillator KaiBC from the photosynthetic bacterium Rhodobacter sphaeroides shed light on the evolution of self-regulating oscillators.
- Warintra Pitsawong
- , Ricardo A. P. Pádua
- & Dorothee Kern
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Article
| Open Access
CFTR function, pathology and pharmacology at single-molecule resolution
A structure–function analysis of cystic fibrosis transmembrane conductance regulator shows its two nucleotide-binding domains dimerize before channel opening, and reveals a mechanism through which conformational changes in the channel regulate chloride conductance.
- Jesper Levring
- , Daniel S. Terry
- & Jue Chen
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Article
| Open Access
Structural basis of mitochondrial membrane bending by the I–II–III2–IV2 supercomplex
A supercomplex comprising all four respiratory chain components contributes to the induction of mitochondrial membrane curvature and tubulation of cristae.
- Alexander Mühleip
- , Rasmus Kock Flygaard
- & Alexey Amunts
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Article
| Open Access
RBFOX2 modulates a metastatic signature of alternative splicing in pancreatic cancer
Analysis of messenger RNA splicing in a large cohort of pancreatic ductal adenocarcinoma tumours identifies differential splicing correlating with disease progression, associated with the the splicing regulator RBFOX2.
- Amina Jbara
- , Kuan-Ting Lin
- & Rotem Karni
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Article |
Structural and mechanistic insights into fungal β-1,3-glucan synthase FKS1
Using cryo-electron microscopy, the molecular architecture and catalytic mechanism of action of the fungal β-1,3-glucan synthase FKS1 are determined.
- Xinlin Hu
- , Ping Yang
- & Hongjun Yu
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Article |
Immunoglobulin M perception by FcμR
The structural basis for the molecular mechanism of recognition of different IgM forms by the IgM receptor FcμR is determined using crystallography and cryo-electron microscopy.
- Yaxin Li
- , Hao Shen
- & Junyu Xiao
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News & Views |
Regrowing tropical forests absorb megatonnes of carbon
An analysis confirms that humid tropical forests recovering from degradation and deforestation absorb substantial amounts of carbon dioxide — but much less than is emitted by the destruction of the original forests.
- Pieter A. Zuidema
- & Catarina C. Jakovac
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Article |
Structural basis of odorant recognition by a human odorant receptor
Through the use of cryo-electron microscopy and molecular dynamics stimulations, mechanistic insight into the binding of an odorant to the human odorant receptor OR51E2 is provided.
- Christian B. Billesbølle
- , Claire A. de March
- & Aashish Manglik
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Technology Feature |
How cell-free processes could speed up vaccine development
Rather than relying on yeast and bacteria, bioengineers are looking for cheaper and easier ways to make proteins and other biomolecules.
- Carrie Arnold
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