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Stepwise requirements for polymerases δ and θ in theta-mediated end joining
Polymerase delta is required for multiple steps in polymerase theta-dependent repair of chromosome breaks, a pathway targeted in cancer therapy.
- Susanna Stroik
- , Juan Carvajal-Garcia
- & Dale A. Ramsden
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Article
| 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
| Open AccessPlant carbonic anhydrase-like enzymes in neuroactive alkaloid biosynthesis
We show how neuroactive alkaloids from clubmosses are biosynthesized, which reveals an unexpected role for carbonic anhydrase-like enzymes in alkaloid scaffold formation.
- Ryan S. Nett
- , Yaereen Dho
- & Elizabeth S. Sattely
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Article |
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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Comment |
‘Oceans are hugely complex’: modelling marine microbes is key to climate forecasts
Microorganisms are the engines that drive most marine processes. Ocean modelling must evolve to take their biological complexity into account.
- Alessandro Tagliabue
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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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Article
| 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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Article
| 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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Book Review |
The plant poisons that shape our daily lives
An exploration of nature’s toxins reveals complex relationships between humans and the plant chemicals we use as foods, medicines and mind-altering drugs.
- Emily Monosson
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News & Views |
Protein condensation regulates water availability in cells
Proteins can condense to form membraneless organelles, which act as vessels for biochemical reactions in cells. An investigation shows that protein condensation is also a cellular mechanism for controlling water availability.
- J. Pedro de Souza
- & Howard A. Stone
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Article
| Open AccessAntiviral type III CRISPR signalling via conjugation of ATP and SAM
The Bacteroides fragilis type III CRISPR protein Cmr conjugates ATP to S-adenosyl methionine, generating S-adenosyl methionine (SAM)-AMP, a novel second messenger with a role in antiviral signalling.
- Haotian Chi
- , Ville Hoikkala
- & Malcolm F. White
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Article
| Open AccessMacromolecular condensation buffers intracellular water potential
Water thermodynamics drive changes in macromolecular assembly that rapidly restore intracellular water availability in response to physiological fluctuations in temperature, pressure and osmotic strength.
- Joseph L. Watson
- , Estere Seinkmane
- & Emmanuel Derivery
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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 & Views |
How purposeless physics underlies purposeful life
Evolution by natural selection peerlessly describes how life’s complexity develops — but can it be explained in terms of physics? A new approach suggests it can.
- George F. R. Ellis
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Article
| 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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Spotlight |
Changing old viticulture for all the right rieslings
Can the French wine industry, built on history and terroir, adapt fast enough to withstand climate change?
- Rachel Nuwer
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Article
| Open AccessUncovering new families and folds in the natural protein universe
The extent to which the AlphaFold database has structurally illuminated proteins that are challenging to annotate for function or putative biological role using standard homology-based approaches at high predicted accuracy is investigated.
- Janani Durairaj
- , Andrew M. Waterhouse
- & Joana Pereira
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Article |
A cross-species proteomic map reveals neoteny of human synapse development
A study presents a cross-species proteomic map of synapse development in neocortex and reveals that the human postsynaptic density assembly develops two to three times slower than that in macaques and mice.
- Li Wang
- , Kaifang Pang
- & Arnold R. Kriegstein
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News & Views |
Previously unknown pathway for lipid biosynthesis discovered
The pathway used by mammalian cells to make triglyceride lipids when supplies of fat molecules are high has long been known. A route that works when fat supplies are low has now been discovered.
- Jean E. Schaffer
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Article
| Open AccessIdentification of an alternative triglyceride biosynthesis pathway
Triacylglycerols are an energy source produced in humans by DGAT1 and DGAT2, but disrupting these enzymes reveals a noncanonical pathway involving the protein DIESL (formerly TMEM68) and its regulator TMX1, which is important during lipid scarcity.
- Gian-Luca McLelland
- , Marta Lopez-Osias
- & Thijn R. Brummelkamp
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Article |
Metabolic programs of T cell tissue residency empower tumour immunity
A study describes the metabolic adaptations supporting differentiation, survival and function of tissue-resident memory CD8+ T cells and how to leverage them to enhance immunity against pathogens and tumours.
- Miguel Reina-Campos
- , Maximilian Heeg
- & Ananda W. Goldrath
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Article
| Open AccessLTP induction by structural rather than enzymatic functions of CaMKII
Several independent lines of evidence demonstrated long-term potentiation induction by a structural function of calmodulin-dependent protein kinase II rather than by its enzymatic activity.
- Jonathan E. Tullis
- , Matthew E. Larsen
- & K. Ulrich Bayer
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Article
| Open AccessA viral ADP-ribosyltransferase attaches RNA chains to host proteins
Bacteriophage T4 uses an enzyme known as ADP-ribosyltransferase ModB to modify the translational apparatus of bacteria it infects, not only by ADP-ribosylating proteins, but also by attaching entire RNA chains in a process known as RNAylation.
- Maik Wolfram-Schauerte
- , Nadiia Pozhydaieva
- & Katharina Höfer
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Article
| Open AccessDirect observation of the conformational states of PIEZO1
The plasma membrane can expand the blades of the PIEZO1 ion channel, impacting channel activation.
- Eric M. Mulhall
- , Anant Gharpure
- & Ardem Patapoutian
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Article
| Open AccessMitochondrial integrated stress response controls lung epithelial cell fate
This study highlights the role of mitochondrial complex I-dependent NAD+ regeneration in directing lung epithelial cell fate during postnatal alveolar development by preventing pathological integrated stress response induction.
- SeungHye Han
- , Minho Lee
- & Navdeep S. Chandel
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Article
| Open AccessTail engagement of arrestin at the glucagon receptor
Structures of the glucagon receptor bound to β-arrestin 1 are reported, providing further information about the arrestin-mediated modulation of G protein-coupled receptors.
- Kun Chen
- , Chenhui Zhang
- & Beili Wu
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News & Views |
Improved theory of ocean iron cycle resolves modelling issues
A revised conceptual model of the chemical and physical forms of iron in the ocean reconciles the mismatch between observations and simulations of the amount of dissolved iron in seawater — and might aid climate predictions.
- Brandy M. Toner
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Article
| Open AccessCentral role of Tim17 in mitochondrial presequence protein translocation
Tim17 contains conserved negative charges close to the intermembrane space side of the bilayer, which are essential to initiate presequence protein translocation along a distinct transmembrane cavity of Tim17 for both classes of preproteins.
- Laura F. Fielden
- , Jakob D. Busch
- & Nils Wiedemann
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Article |
Oligomerization-mediated activation of a short prokaryotic Argonaute
Cryo-electron microscopy structures and biochemical analyses provide insight into how short prokaryotic Argonaute proteins are assembled and activated, and reveal that oligomerization has a key role in driving catalytic activity.
- Zhangfei Shen
- , Xiao-Yuan Yang
- & Tian-Min Fu
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Article |
Structure of an endogenous mycobacterial MCE lipid transporter
Proteins of the Mycobacterium smegmatis Mce1 system assemble to form an elongated ABC transporter complex that is long enough to span the impermeable mycobacterial cell envelope.
- James Chen
- , Alice Fruhauf
- & Damian C. Ekiert
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News & Views |
Sixty years since the report of global lead pollution
The 1963 discovery that even the vast oceans were highly contaminated with lead from car exhausts sparked debate and policy changes that benefited the health of millions — and revolutionized the practices of marine biogeochemistry.
- Jerome Nriagu
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News |
Dementia risk linked to blood-protein imbalance in middle age
Abnormal levels of certain proteins — many of which have roles outside the brain — could be an early hallmark of Alzheimer’s disease or similar conditions.
- Lilly Tozer
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Research Briefing |
Protein folding stability measured at scale
Protein sequences vary widely in their folding stabilities (the energetic favourability of folded compared with unfolded conformations), and protein alterations that affect stability have profound effects on evolution, health and disease, and biotechnological applications. An innovative method has made it possible to measure these stabilities on a massive scale, revealing evolutionary trends and opening up possibilities for machine learning.
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Article
| Open AccessMega-scale experimental analysis of protein folding stability in biology and design
Large-scale assays using cDNA display proteolysis are used to measure the folding stabilities of protein domains, providing a method to quantify the effects of mutations on protein folding, with applications in protein design.
- Kotaro Tsuboyama
- , Justas Dauparas
- & Gabriel J. Rocklin
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News Feature |
AI tools are designing entirely new proteins that could transform medicine
Digital art techniques can now devise custom, working biomolecules on demand.
- Ewen Callaway
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Article
| Open AccessDe novo design of protein structure and function with RFdiffusion
Fine-tuning the RoseTTAFold structure prediction network on protein structure denoising tasks yields a generative model for protein design that achieves outstanding performance on a wide range of protein structure and function design challenges.
- Joseph L. Watson
- , David Juergens
- & David Baker
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Article |
Hepatitis C virus RNA is 5′-capped with flavin adenine dinucleotide
Hepatitis C virus utilizes flavin adenine dinucleotide as a non-canonical initiating nucleotide for the viral RNA polymerase, resulting in 5′ capping of viral RNA, which provides protection against the host innate immune response.
- Anna V. Sherwood
- , Lizandro R. Rivera-Rangel
- & Jeppe Vinther
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Matters Arising |
DHODH inhibitors sensitize to ferroptosis by FSP1 inhibition
- Eikan Mishima
- , Toshitaka Nakamura
- & Marcus Conrad
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Research Briefing |
World’s largest ocean ‘dead zone’ was well oxygenated during past warm period
The eastern tropical Pacific Ocean, which today is a major oxygen-deficient zone, or ‘dead zone’, was well oxygenated during the Miocene warm period about 16 million years ago. This finding supports model simulations suggesting that modern oxygen loss from the ocean might eventually reverse.
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Article
| Open AccessFanzor is a eukaryotic programmable RNA-guided endonuclease
Fanzor is shown to be an RNA-guided DNA endonuclease, demonstrating that such endonucleases are found in all domains of life and indicating a potential new tool for genome engineering applications.
- Makoto Saito
- , Peiyu Xu
- & Feng Zhang
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Article
| Open AccessPhase separation of FSP1 promotes ferroptosis
An inhibitor of the ferroptosis-suppressing FSP1 induces phase separation of FSP1, thereby impairing its function and reducing tumour growth.
- Toshitaka Nakamura
- , Clara Hipp
- & Marcus Conrad
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Article |
Structural insights into BCDX2 complex function in homologous recombination
Analyses of the structure and biochemical properties of the tetrameric complex of RAD51B, RAD51C, RAD51D and XRCC2 reveal details of its role in the repair of DNA double-strand breaks.
- Yashpal Rawal
- , Lijia Jia
- & Shaun K. Olsen
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Article
| Open AccessRelaxed targeting rules help PIWI proteins silence transposons
Of the two types of Argonaute proteins produced by animals, AGO and PIWI, PIWI proteins can bind RNAs with less complementarity, enabling efficient silencing of transposons without the need to produce new RNA guides.
- Ildar Gainetdinov
- , Joel Vega-Badillo
- & Phillip D. Zamore
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Article |
Structural basis of mitochondrial protein import by the TIM23 complex
The cryo-electron microscopy structure of the mitochondrial TIM23 complex from Saccharomyces cerevisiae shows that Tim17 forms a protein translocation path.
- Sue Im Sim
- , Yuanyuan Chen
- & Eunyong Park
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Technology Feature |
How scientists are hacking the genetic code to give proteins new powers
By modifying the blueprint of life, researchers are endowing proteins with chemistries they’ve never had before.
- Diana Kwon
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Article |
Structural basis for the binding of DNP and purine nucleotides onto UCP1
Using cryo-electron microscopy, the structures of human UCP1 in the nucleotide-free state, the DNP activator-bound state, and the inhibitory ATP-bound state are resolved, providing details of how purine nucleotides inhibit UCP1.
- Yunlu Kang
- & Lei Chen
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Article |
Break-induced replication orchestrates resection-dependent template switching
Break-induced telomere synthesis initiates recruitment of the SNM1A nuclease, which promotes DNA end resection that in turn allows template switching to enable bypass of lesions.
- Tianpeng Zhang
- , Yashpal Rawal
- & Roger A. Greenberg
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Article
| Open AccessGenome 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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