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AlphaFold is five years old — these charts show how it revolutionized scienceSince it was unveiled in 2020, Google DeepMind’s game-changing AI tool has helped researchers all over the world to predict the 3D structures of hundreds of millions of proteins.
- Ewen Callaway
Article
|Open Access
ZAK activation at the collided ribosomeThe kinase ZAK is activated at collided ribosomes to mediate the ribotoxic stress response.
- Vienna L. Huso
- ,Shuangshuang Niu
- & Roland Beckmann
Article
|Open Access
Structural basis of regulated N-glycosylation at the secretory transloconThe structural mechanism of a natively isolated GRP94 folding intermediate tethered to a CCDC134-bound translocon is described, revealing how the nascent chain remodels the translocon to control N-glycosylation by OST.
- Melvin Yamsek
- ,Mengxiao Ma
- & Robert J. Keenan
News Feature |
Google DeepMind won a Nobel prize for AI: can it produce the next big breakthrough?The company was created to use AI for world- changing science — and achieved that with AlphaFold. But the advent of large language models raises deep questions about the future of DeepMind.
- Elizabeth Gibney
Article |
Potent neutralization of Marburg virus by a vaccine-elicited antibody
- Amin Addetia
- ,Lisa Perruzza
- & David Veesler
Article |
In situ structural mechanism of epothilone-B-induced CNS axon regenerationA combined cryo-electron tomography and cryo-electron microscopy pipeline was developed to inflict axonal damage and monitor the cellular response induced by epothilone B, revealing that microtubule polymerization at and beyond the lesion site promote axon regeneration.
- Satish Bodakuntla
- ,Kenichiro Taira
- & Naoko Mizuno
Article |
An ATP-gated molecular switch orchestrates human messenger RNA export
- Ulrich Hohmann
- ,Max Graf
- & Clemens Plaschka
Article
|Open Access
Synthetic α-synuclein fibrils replicate in mice causing MSA-like pathologySynthetic fibril strain 1B is a pathogen that is capable of self-replication and inducing glial cytoplasmic inclusions in vivo in mice, and the structural features of 1B may underlie the pathology of individuals with multiple-system atrophy.
- Domenic Burger
- ,Marianna Kashyrina
- & François Ichas
Article
|Open Access
Atomically accurate de novo design of antibodies with RFdiffusionThe combination of computational design, laboratory-based screening and biophysical validation enables the de novo generation of variable heavy-chain antibody fragments and antibodies that precisely target chosen disease-related molecules.
- Nathaniel R. Bennett
- ,Joseph L. Watson
- & David Baker
Article
|Open Access
Structural snapshots capture nucleotide release at the μ-opioid receptorStructures of GDP-bound MOR–Gi conformational states combined with pharmacological assays show an inverse correlation between ligand efficacy and GDP affinity, where agonists decrease GDP affinity, promoting GTP exchange, and antagonists increase GDP affinity, dampening activation, thus providing structural and mechanistic insights into G protein activation.
- Saif Khan
- ,Aaliyah S. Tyson
- & Cornelius Gati
Article
|Open Access
Helicase-mediated mechanism of SSU processome maturation and disassemblyStructural studies of 16 native yeast ribosomal small subunit processome structures provide insights into the mechanisms governing the transformation into a pre-40S particle.
- Olga Buzovetsky
- & Sebastian Klinge
Article |
Mechanism of conductance control and neurosteroid binding in NMDA receptorsIon-channel conductance levels are controlled by the bending patterns of pore-forming transmembrane helices in the heterotetrameric neuronal channel GluN1a-2BN-methyl-D-aspartate receptor.
- Hyunook Kang
- ,Ruben Steigerwald
- & Hiro Furukawa
News |
Open-source protein structure AI aims to match AlphaFoldThe developers of OpenFold3 have released an early version of the tool, which they hope will one day perform on par with DeepMind’s protein-structure model.
- Miryam Naddaf
Research Briefing |
Elaborate machinery for inserting proteins into the outer membrane of bacteriaBacteria insert proteins into their outer membrane using a highly conserved apparatus known as the β-barrel assembly machinery (BAM). A large group of bacteria with particularly complex outer-membrane proteins is now shown to have a BAM apparatus with a highly unusual composition.
Article
|Open Access
A new paradigm for outer membrane protein biogenesis in the BacteroidotaStructural and biochemical studies of the β-barrel-assembly machinery fromFlavobacterium johnsoniae reveal a subunit composition and assembly that are distinct from those of the canonicalEscherichia coli complex.
- Xiaolong Liu
- ,Luis Orenday Tapia
- & Ben C. Berks
Article
|Open Access
The Panoptes system uses decoy cyclic nucleotides to defend against phageThe Panoptes antiphage system defends bacteria by detecting phage-encoded counter-defences that sequester cyclic nucleotide signals, triggering membrane disruption and highlighting a broader strategy of sensing immune evasion through second-messenger surveillance.
- Ashley E. Sullivan
- ,Ali Nabhani
- & Benjamin R. Morehouse
Article
|Open Access
Design of facilitated dissociation enables timing of cytokine signallingA fresh approach to protein design that incorporates excited intermediate states enables precise control over the lifetime of protein interactions, with potential applications in cell-signalling modulation and in biosensors and synthetic circuits.
- Adam J. Broerman
- ,Christoph Pollmann
- & David Baker
Article
|Open Access
Myeloperoxidase transforms chromatin into neutrophil extracellular trapsMyeloperoxidase, a highly expressed neutrophil protein, disassembles nucleosomes, facilitating neutrophil extracellular trap (NET) formation, and binds stably to NETs extracellularly.
- Garth Lawrence Burn
- ,Tobias Raisch
- & Arturo Zychlinsky
Article
|Open Access
Structural basis for mTORC1 activation on the lysosomal membraneCryo-electron microscopy was used to study human mechanistic target of rapamycin complex 1 (mTORC1) activation on lysosomal membranes, showing progressive recruitment by RAG–Ragulator, RHEB and RAPTOR, culminating in mTOR–membrane engagement and full enzyme activation.
- Zhicheng Cui
- ,Alessandra Esposito
- & James H. Hurley
Article
|Open Access
Delta-type glutamate receptors are ligand-gated ion channelsStructural and in vitro functional studies of the human delta-type ionotropic glutamate receptor GluD2 reveal that it contains an ion channel that is activated byd-serine and GABA (γ-aminobutyric acid).
- Haobo Wang
- ,Fairine Ahmed
- & Edward C. Twomey
Article
|Open Access
Structure and mechanism of the mitochondrial calcium transporter NCLXCryogenic electron microscopy structures and functional analyses reveal that NCLX functions as a H+/Ca2+ rather than a Na+/Ca2+ exchanger, and uncover its transport mechanism with implications for therapies treating cardiac and neurodegenerative disorders related to abnormal mitochondrial Ca2+.
- Minrui Fan
- ,Chen-Wei Tsai
- & Liang Feng
Article
|Open Access
A nanobody specific to prefusion glycoprotein B neutralizes HSV-1 and HSV-2A neutralizing nanobody specific to the prefusion conformation of herpes simplex virus glycoprotein B has cross-species activity and offers insights into virus neutralization, possible immunogens and an attractive avenue for antiviral interventions.
- Benjamin Vollmer
- ,Henriette Ebel
- & Kay Grünewald
Research Briefing |
A closer look at how cells sense dietary nutrientsCells need to sense the presence or absence of nutrients so that they can adjust their metabolism and growth accordingly. A key node in cellular nutrient sensing is the protein complex GATOR2. The mechanisms of how two nutrient-sensing proteins bind to and alter the configuration of GATOR2 have been determined.
Article |
Crystal structures of agonist-bound human cannabinoid receptor CB1Crystal structures of human CB1 bound to two cannabinoid agonists reveal key features, including a twin toggle switch and binding pocket reduction, advancing understanding of receptor dynamics and guiding cannabinoid drug design.
- Tian Hua
- ,Kiran Vemuri
- & Zhi-Jie Liu
Article
|Open Access
Structural basis for the dynamic regulation of mTORC1 by amino acidsUsing cryo-electron microscopy, the interactions of Sestrin2 and CASTOR1 with GATOR2 were resolved, revealing how mTORC1 activation is regulated and how nutrient availability triggers signalling for cellular growth.
- Max L. Valenstein
- ,Maximilian Wranik
- & Kacper B. Rogala
Article
|Open Access
Molecular mechanism of ultrafast transport by plasma membrane Ca2+-ATPasesStructural insights into ultrafast Ca2+ transport by plasma membrane Ca2+-ATPases are provided, highlighting an essential role for PtdIns(4,5)P2 dynamics.
- Deivanayagabarathy Vinayagam
- ,Oleg Sitsel
- & Stefan Raunser
Article
|Open Access
SLC45A4 is a pain gene encoding a neuronal polyamine transporterTheSLC45A4 gene encodes a neuronal polyamine transporter and is linked to pain response in humans and mice.
- Steven J. Middleton
- ,Sigurbjörn Markússon
- & David L. Bennett
Article |
Discovery of a widespread chemical signalling pathway in the BacteroidotaTheN-acyl-cyclolysine system regulates the expression of co-localized operons encoding diverse secreted molecules in Bacteroidota.
- Luis Linares-Otoya
- ,Jaden D. Shirkey
- & Mohamed S. Donia
Article
|Open Access
Structural basis of fast N-type inactivation in Kv channelsThis paper explores how voltage-gated potassium channels can plug the pore to prevent the conductance of ions during inactivation.
- Xiao-Feng Tan
- ,Ana I. Fernández-Mariño
- & Kenton J. Swartz
Article
|Open Access
Programmable protein ligation on cell surfacesA synthetic biology system called SMART has been developed that uses conditional protein splicing for the programmable ligation of functional proteins from previously defined molecular combinations on cell surfaces.
- Christian Kofoed
- ,Girum Erkalo
- & Tom W. Muir
Article |
SuFEx-based antitubercular compound irreversibly inhibits Pks13A preclinical covalent compound, CMX410, contains a aryl fluorosulfate warhead that targets the acyltransferase domain ofMtb Pks13, an essential enzyme in cell-wall biosynthesis, making it a promising candidate for tuberculosis treatment regimens.
- Inna V. Krieger
- ,Paridhi Sukheja
- & Case W. McNamara
Article |
How short peptides disassemble tau fibrils in Alzheimer’s diseaseCryo-electron and atomic force microscopy shed light on how fibrils of the protein tau, which accumulate in the brain of people with Alzheimer’s disease, can be disassembled by short peptides, providing a possible route towards developing treatments.
- Ke Hou
- ,Peng Ge
- & David S. Eisenberg
Article
|Open Access
Loss of FCoV-23 spike domain 0 enhances fusogenicity and entry kineticsThe molecular mechanisms of cell entry for the recently identified highly pathogenic feline coronavirus FCoV-23 are characterized in detail.
- M. Alejandra Tortorici
- ,Annette Choi
- & David Veesler
Article
|Open Access
The role of metabolism in shaping enzyme structures over 400 million yearsBy combining structural biology and evolutionary genomics analyses, the evolution of enzymes over 400 million years is shown to be governed by catalytic function, metabolic network architecture, cost and molecular interactions.
- Oliver Lemke
- ,Benjamin Murray Heineike
- & Markus Ralser
Article
|Open Access
Electron flow in hydrogenotrophic methanogens under nickel limitationTwo distantly related methanogens shift the methanogenic pathway under nickel limitation, suggesting that methanogens adapt to changing bioavailability of nickel by rerouting electron flow between two different pathways.
- Shunsuke Nomura
- ,Pablo San Segundo-Acosta
- & Seigo Shima
Article
|Open Access
Architecture, dynamics and biogenesis of GluA3 AMPA glutamate receptorsThe GluA3 homomer substantially diverges from other AMPA-type glutamate receptors.
- Aditya Pokharna
- ,Imogen Stockwell
- & Ingo H. Greger
Article
|Open Access
Interactions between TTYH2 and APOE facilitate endosomal lipid transferThe Tweety homologue TTYH2 is identified as the lipid transfer mediator for APOE-containing lipoproteins.
- Anastasiia Sukalskaia
- ,Andreas Karner
- & Raimund Dutzler
Article |
Structural and functional characterization of human sweet taste receptorCryo-electron microscopy structures of the human sweet taste receptor in the apo and sucralose-bound states reveal its heterodimeric architecture and mechanisms of ligand binding and signal activation.
- Zongjun Shi
- ,Weixiu Xu
- & Tian Hua
Article
|Open Access
Gating and noelin clustering of native Ca2+-permeable AMPA receptorsCryo-electron microscopy analyses of calcium-permeable AMPA receptors from rat brain show that they are composed primarily of GluA1 and GluA4 subunits, and biochemical studies show that noelin promotes inter-receptor interactions without modulating receptor function.
- Chengli Fang
- ,Cathy J. Spangler
- & Eric Gouaux
Article
|Open Access
Complete computational design of high-efficiency Kemp elimination enzymesWe present a computational approach to the design of high-efficiency enzymes with catalytic parameters comparable to natural enzymes, enabling programming of stable, high-efficiency, new-to-nature Kemp elimination enzymes through minimal experimental effort.
- Dina Listov
- ,Eva Vos
- & Sarel J. Fleishman
Article |
Allosteric modulation and biased signalling at free fatty acid receptor 2Structural, pharmacological and computational studies reveal how different classes of positive allosteric modulators bind to distinct allosteric sites and use noncanonical mechanisms to activate the free-fatty acid receptor FFA2.
- Xuan Zhang
- ,Abdul-Akim Guseinov
- & Cheng Zhang
Technology Feature |
Freeze frame: cracking molecular motionTime-resolved cryo-electron microscopy can resolve protein motion on millisecond or even microsecond timescales, but the need for highly specialized tools and skills limits the method’s reach.
- Michael Eisenstein
Article |
Cryo-EM structure of a natural RNA nanocageThree-dimensional structures of two natural RNA nanocages reveal unique quaternary structures without the contribution of proteins.
- Xiaobin Ling
- ,Dmitrij Golovenko
- & Wenwen Fang
Article |
Dynamic assemblies and coordinated reactions of non-homologous end joiningStructures associated with the final steps of non-homologous end joining (NHEJ) and gap filling present new targets for NHEJ inhibition to enhance efficacy of radiotherapy and accuracy of gene editing.
- Lan Liu
- ,Jun Li
- & Wei Yang
Article |
Structural insights into human Pol III transcription initiation in actionReconstitution of seven human RNA polymerase III (Pol III) transcribing complexes (TC4/5/6/8/10/12/13) halted on U6 promoters with nascent RNAs of 4–13 nucleotides offers molecular insights into Pol III dynamics.
- Qianmin Wang
- ,Yulei Ren
- & Yanhui Xu
Article |
Subnucleosome preference of human chromatin remodeller SMARCAD1Human chromatin remodeller SMARCAD1 exhibits a substrate preference for subnucleosomal particles over the canonical nucleosome.
- Pengjing Hu
- ,Jingxi Sun
- & Zhucheng Chen
Article |
Protein-primed homopolymer synthesis by an antiviral reverse transcriptaseA bacterial reverse transcriptase synthesizes polydeoxyadenylate to provide population-level immunity against viral infection.
- Stephen Tang
- ,Rimantė Žedaveinytė
- & Samuel H. Sternberg
Article
|Open Access
Stepwise ATP translocation into the endoplasmic reticulum by human SLC35B1SLC35B1, initially thought to be a nucleotide sugar transporter, is an essential ATP/ADP exchanger that imports ATP into the endoplasmic reticulum through a unique stepwise translocation mechanism.
- Ashutosh Gulati
- ,Do-Hwan Ahn
- & David Drew
Article |
Effect of phosphorylation barcodes on arrestin binding to a chemokine receptorDifferent phosphorylation patterns created by GRK2 and GRK5 on the C-terminal tail of ACKR3 lead to distinct structural arrangements and dynamics of G-protein-coupled receptor–arrestin complexes, potentially explaining diverse cellular outcomes.
- Qiuyan Chen
- ,Christopher T. Schafer
- & John J. G. Tesmer
News |
I told AI to make me a protein. Here’s what it came up withA new crop of artificial-intelligence models allows users to create, manipulate and learn about biology using ordinary language.
- Ewen Callaway
