Research Highlight |
Featured
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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 AccessFrom 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 AccessCFTR 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 AccessStructural 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 AccessRBFOX2 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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Article |
Macrophage fumarate hydratase restrains mtRNA-mediated interferon production
Inhibition of the tricarboxylic acid cycle enzyme fumarate hydratase leads to deregulation of cytokine production in macrophages, which has implications in human diseases such as systemic lupus erythematosus.
- Alexander Hooftman
- , Christian G. Peace
- & Luke A. J. O’Neill
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Article
| Open AccessStructural basis for bacterial energy extraction from atmospheric hydrogen
Structural and biochemical studies of the Mycobacterium smegmatis hydrogenase Huc provides insights into how [NiFe] hydrogenases oxidize trace amounts of atmospheric hydrogen and transfer the electrons liberated via quinone transport.
- Rhys Grinter
- , Ashleigh Kropp
- & Chris Greening
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Article
| Open AccessFumarate induces vesicular release of mtDNA to drive innate immunity
Fumarate metabolism regulates the innate immune response through a mechanism in which high levels of fumarate result in the generation of mitochondrial-derived vesicles and the release of mitochondrial DNA into the cytosol, which activates inflammatory pathways.
- Vincent Zecchini
- , Vincent Paupe
- & Christian Frezza
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Article |
Nucleolar URB1 ensures 3′ ETS rRNA removal to prevent exosome surveillance
A high-resolution microscopy screen of candidate nucleolar proteins identifies URB1 as a protein that is confined to the periphery of the dense fibrillar component, with key roles in pre-ribosomal RNA folding and processing.
- Lin Shan
- , Guang Xu
- & Ling-Ling Chen
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Technology Feature |
Astrobiologists train an AI to find life on Mars
An artificial-intelligence model trialled in Chile’s Atacama Desert could one day detect signs of life on other planets.
- Amanda Heidt
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Article
| Open AccessDe novo design of luciferases using deep learning
A deep-learning-based strategy is used to design artificial luciferases that catalyse the oxidative chemiluminescence of diphenylterazine with high substrate specificity and catalytic efficiency.
- Andy Hsien-Wei Yeh
- , Christoffer Norn
- & David Baker
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Article
| Open AccessA NPAS4–NuA4 complex couples synaptic activity to DNA repair
A neuron-specific activity-dependent DNA repair mechanism is identified, the impairment of which may lead to neurodevelopmental disorders, neurodegeneration and ageing.
- Elizabeth A. Pollina
- , Daniel T. Gilliam
- & Michael E. Greenberg
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Article
| Open AccessBiomolecular analyses enable new insights into ancient Egyptian embalming
Philological analysis of labels and instructions, together with gas chromatography–mass spectrometry analysis of residues on vessels recovered from a 26th Dynasty embalming workshop at Saqqara, Egypt provide insights into ancient Egyptian embalming practices.
- Maxime Rageot
- , Ramadan B. Hussein
- & Philipp W. Stockhammer
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Article |
mRNA ageing shapes the Cap2 methylome in mammalian mRNA
Cap2 methylation increases on transcripts as they age, reducing activation of innate immunity.
- Vladimir Despic
- & Samie R. Jaffrey
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Article |
Slow TCA flux and ATP production in primary solid tumours but not metastases
As solid tumours develop, cancer cells shed energetically expensive tissue-specific functions, enabling uncontrolled growth despite a limited ability to produce ATP.
- Caroline R. Bartman
- , Daniel R. Weilandt
- & Joshua D. Rabinowitz
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Article |
Structural basis for substrate selection by the SARS-CoV-2 replicase
Cryo-EM is used to visualize the SARS-CoV-2 RTC bound to each of the natural NTPs as well as remdesivir triphosphate (RDV-TP) in states poised for incorporation, explaining the interactions required for NTP recognition and RDV-TP selectivity.
- Brandon F. Malone
- , Jason K. Perry
- & Seth A. Darst
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News & Views |
Bacterial defence repurposed to fight blight
The discovery of bacterial compounds that have antifungal properties opens up opportunities for the development of agents that protect crops from a devastating disease.
- Andrew Mitchinson
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Article |
Architecture of chloroplast TOC–TIC translocon supercomplex
A cryo-electron microscopy analysis of the Chlamydomonas reinhardtii TOC–TIC supercomplex reveals that Tic214 traverses the chloroplast inner membrane, the intermembrane space and the outer membrane, connecting the TOC complex with the TIC proteins.
- Hao Liu
- , Anjie Li
- & Zhenfeng Liu
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Research Briefing |
A census of complexes formed by mitochondrial proteins
Mitochondria are intracellular organelles that contain a large set of proteins to help them produce energy, among other functions. A systematic analysis reveals how mitochondrial proteins are organized into complexes and assemblies, facilitating the identification of the molecular mechanisms and pathways that underlie the organelle’s many functions.
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Article
| Open AccessVisualization of translation and protein biogenesis at the ER membrane
Structural studies of the ribosome-associated endoplasmic reticulum translocon complex based on cryo-electron tomography and molecular modelling reveal multiple intermediate states and interactions between the components of the complex and its cofactors.
- Max Gemmer
- , Marten L. Chaillet
- & Friedrich Förster
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Article
| Open AccessInsulin-regulated serine and lipid metabolism drive peripheral neuropathy
Serine deficiency can increase small fibre neuropathy in wild-type mice and serine replacement in diabetic mice alleviates diabetic neuropathy, directly linking amino acid metabolism to peripheral nerve disorders.
- Michal K. Handzlik
- , Jivani M. Gengatharan
- & Christian M. Metallo
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Article |
A molecular network of conserved factors keeps ribosomes dormant in the egg
Mass spectrometry and structural studies demonstrate the specific changes in protein composition that accompany the transition of ribosomes in zebrafish and Xenopus eggs from a dormant to an active state during early embryogenesis.
- Friederike Leesch
- , Laura Lorenzo-Orts
- & Andrea Pauli
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News |
Trial settles debate over best design for mRNA in COVID vaccines
The biggest defender of ‘unmodified’ mRNA for vaccines against infectious disease has a change of heart.
- Elie Dolgin
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Article
| Open AccessAn atlas of substrate specificities for the human serine/threonine kinome
Analysis of the kinase activity of 300 protein Ser/Thr kinases reveals that the substrate specificity of the kinome is substantially more diverse than expected and is driven extensively by negative selectivity
- Jared L. Johnson
- , Tomer M. Yaron
- & Lewis C. Cantley
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Article |
Structural basis for intrinsic transcription termination
Structural studies of Escherichia coli transcription intrinsic termination complexes representing distinct intermediates using cryo-electron microscopy provide insights into the steps and mechanism of transcription termination.
- Linlin You
- , Expery O. Omollo
- & Yu Zhang
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Article
| Open AccessRNA targeting unleashes indiscriminate nuclease activity of CRISPR–Cas12a2
Structural analysis of Cas12a2, a CRISPR-associated nuclease that nonspecifically cleaves ssRNA, ssDNA and dsDNA, reveals a complete activation pathway involved in the abortive infection system protecting cells against invasion.
- Jack P. K. Bravo
- , Thomson Hallmark
- & David W. Taylor
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News & Views |
How to feed the world while reducing nitrogen pollution
An analysis of more than 1,500 field observations has identified a collection of agricultural practices that can improve the use of nitrogen fertilizers — boosting crop yields while reducing environmental pollution.
- Longlong Xia
- & Xiaoyuan Yan
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Article
| Open AccessStructural basis of broad-spectrum β-lactam resistance in Staphylococcus aureus
Cryo-electron microscopy structures of Staphylococcus aureus BlaR1 reveal dynamic signalling states regulating broad spectrum β-lactam antibiotic resistance through cleavage of the transcriptional repressor BlaI and induced expression of the β-lactamase blaZ and the β-lactam-resistant cell-wall transpeptidase mecA.
- J. Andrew N. Alexander
- , Liam J. Worrall
- & Natalie C. J. Strynadka
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Article |
Structures and mechanisms of tRNA methylation by METTL1–WDR4
Using cryo-electron microscopy, structural and mechanistic insights into how the METTL1–WDR4 complex catalyses methylation of tRNAs are shown.
- Victor M. Ruiz-Arroyo
- , Rishi Raj
- & Yunsun Nam
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Article
| Open AccessCas12a2 elicits abortive infection through RNA-triggered destruction of dsDNA
RNA targeting by the Sulfuricurvum type V single-effector nuclease SuCas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA—after recognition of an RNA target through an activating protospacer-flanking sequence, SuCas12a2 efficiently degrades ssRNA, ssDNA and dsDNA.
- Oleg Dmytrenko
- , Gina C. Neumann
- & Chase L. Beisel
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Article |
Structural basis of regulated m7G tRNA modification by METTL1–WDR4
Structures of the human METTL1–WDR4 complex are revealed, providing molecular insights into substrate recognition, modification and catalytic regulation by the N7-methylguanosine methyltransferase complex.
- Jiazhi Li
- , Longfei Wang
- & Richard I. Gregory
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News & Views |
Cause of the 2020 surge in atmospheric methane clarified
Atmospheric methane concentrations rose unexpectedly during the lockdowns of 2020. It now seems that this was due to warm, wet weather in the Northern Hemisphere and, ironically, a slowdown in air-pollutant emissions.
- George H. Allen
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Article
| Open AccessPrinciples of mitoribosomal small subunit assembly in eukaryotes
The structures of both human and yeast mitochondrial ribosomal small subunits undergoing assembly are uncovered.
- Nathan J. Harper
- , Chloe Burnside
- & Sebastian Klinge
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Article
| Open AccessStructures of the holo CRISPR RNA-guided transposon integration complex
Structural studies of the CRISPR-associated transposon comprising Cas12k, TnsC, TnsB and TniQ from Scytonema hofmannii using cryo-electron microscopy reveal insights into the architecture and mechanism of RNA-guided DNA transposition.
- Jung-Un Park
- , Amy Wei-Lun Tsai
- & Elizabeth H. Kellogg
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Article |
Antiviral signalling by a cyclic nucleotide activated CRISPR protease
A CalpL–CalpT–CalpS cascade mediated by cyclic oligoadenylates is identified as a mechanism to detect viral RNA and activate subsequent antivirus responses in microorganisms.
- Christophe Rouillon
- , Niels Schneberger
- & Gregor Hagelueken
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Article
| Open AccessStructural basis of tankyrase activation by polymerization
Structural insights into the poly-ADP-ribosyltransferase tankyrase reveal its filamentous architecture and illustrate how assembly controls catalytic and non-catalytic functions.
- Nisha Pillay
- , Laura Mariotti
- & Sebastian Guettler
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Career Column |
‘Moms in Proteomics’ pushes for change
A need for community drove Jennifer Geddes-McAlister to found a network for mothers in science. Here’s what she learnt.
- Jennifer Geddes-McAlister
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Where I Work |
Braving stings to put jellyfish on the menu
Antonella Leone catches jellyfish off the coast of Italy to study them as potential sources of medicine and food.
- James Mitchell Crow
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Research Briefing |
Peat decomposition in central Congo was triggered by a drying climate
The world’s largest tropical peatland complex is in the central Congo Basin. A drying of the climate between 5,000 and 2,000 years ago triggered decomposition of peat in the Congo Basin and emission of carbon into the atmosphere. The tipping point at which drought results in carbon release might accelerate future climate change if regional droughts become more common.
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News |
AlphaFold’s new rival? Meta AI predicts shape of 600 million proteins
Microbial molecules from soil, seawater and human bodies are among the planet’s least understood.
- Ewen Callaway
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Article |
Bestrophin-2 and glutamine synthetase form a complex for glutamate release
Electrophysiological, structural and biochemical studies on the bestrophin-2 anion channel reveal asymmetric permeability to glutamate and show that it forms a cooperative machinery in complex with glutamine synthetase for glutamate release.
- Aaron P. Owji
- , Kuai Yu
- & Tingting Yang
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