Featured
-
-
Article
| Open AccessBioinformatics leading to conveniently accessible, helix enforcing, bicyclic ASX motif mimics (BAMMs)
Researchers mimic protein interface helices by stapling peptide side chains, or replacing hydrogen bonds with covalent ones, and synthetic helical mimics are heavily biased towards stapling. Here the authors describe bioinformatic discovery of hydrophobic triangles at helix N-termini, and rigid, bicyclic synthetic mimics of them.
- Tianxiong Mi
- , Duyen Nguyen
- & Kevin Burgess
-
Article
| Open AccessThe 8-17 DNAzyme can operate in a single active structure regardless of metal ion cofactor
Here, the authors use solution-state NMR to characterize the structure of 8–17 DNAzyme, revealing that all metal cofactors induce the same DNAzyme fold in contrast to previous findings.
- Julia Wieruszewska
- , Aleksandra Pawłowicz
- & Witold Andrałojć
-
Article
| Open AccessExon-junction complex association with stalled ribosomes and slow translation-independent disassembly
Bensaude et al. use a split luciferase approach to show that exon-junction complex assembly and disassembly occur faster when they are translation-dependent than when they are translation-independent; and they uncover an association with ribosomes.
- Olivier Bensaude
- , Isabelle Barbosa
- & Hervé Le Hir
-
Article
| Open AccessStructure of HIV-1 RRE stem-loop II identifies two conformational states of the high-affinity Rev binding site
HIV relies on the RRE RNA interaction with Rev protein for nuclear export of viral mRNAs. The structure of the high-affinity Rev binding site in RRE in two conformations suggests a mechanism for initial Rev binding and oligomerization onto RRE.
- Jerricho Tipo
- , Keerthi Gottipati
- & Kyung H. Choi
-
Article
| Open AccessAccelerating reliable multiscale quantum refinement of protein–drug systems enabled by machine learning
Biomacromolecule structures are vital for drug design. Here, the authors integrate one or two machine learning potentials in an ONIOM-based quantum refinement method, achieving reliable drug structures at an QM level in proteins with high efficiency.
- Zeyin Yan
- , Dacong Wei
- & Lung Wa Chung
-
Article
| Open AccessExtracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation
K2P channels are important regulators of cellular electrical activity. Here the authors show how nanobody fragments can be used to detect and modulate TREK2 K2P channel activity to provide insight into the mechanism of gating.
- Karin E. J. Rödström
- , Alexander Cloake
- & Stephen J. Tucker
-
Article
| Open AccessThe EV71 2A protease occupies the central cleft of SETD3 and disrupts SETD3-actin interaction
Enteroviruses are responsible for several human diseases without treatment. This study describes the molecular interactions between SETD3, actin, and viral 2A in viral replication, providing a framework for the development of host-targeted therapies against enteroviruses.
- Xiaopan Gao
- , Bei Wang
- & Sheng Cui
-
Article
| Open AccessMycobacterial biotin synthases require an auxiliary protein to convert dethiobiotin into biotin
Lipid biosynthesis in the pathogen M. tuberculosis depends on biotin for posttranslational modification of key enzymes. Here, Qu et al. identify an auxiliary protein that is required by M. tuberculosis to synthesize biotin.
- Di Qu
- , Peng Ge
- & Dirk Schnappinger
-
Article
| Open AccessStructure, mechanism, and evolution of the last step in vitamin C biosynthesis
Photosynthetic organisms, fungi, and animals contain distinct pathways for vitamin C biosynthesis, but the final biosynthetic step consistently involves an oxidation reaction catalysed by the aldonolactone oxidoreductases. Here, the authors investigate the origin and evolution of the diversified activities and substrate preferences featured by these enzymes using different methods and find evidence that they share a common ancestor.
- Alessandro Boverio
- , Neelam Jamil
- & Andrea Mattevi
-
Article
| Open AccessSequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity
Here, the authors show that GalNAc-T3 and T7 regulate furin cleavage of the SARS-CoV-2 spike protein via O-glycosylation. This influences viral assembly and infection, highlighting glycosylation as a host defense mechanism.
- Shengjun Wang
- , Wei Ran
- & Yang Mao
-
Article
| Open AccessSer/Leu-swapped cell-free translation system constructed with natural/in vitro transcribed-hybrid tRNA set
The use of orthogonal genetic code can help to prevent the escape of hazardous genes through horizontal gene transfer. Here, the authors develop a cell-free translation system with the Ser/Leu-swapped genetic code using a hybrid tRNA set and show its application in enhancing the production of superfolder GFP.
- Tomoshige Fujino
- , Ryogo Sonoda
- & Hiroshi Murakami
-
Article
| Open AccessCryo-EM structures of the human Elongator complex at work
Here the authors determined several cryo-EM structures of the human Elongator complex, which modifies anticodons of tRNAs. The structural work is complemented by functional analyses to understand this clinically relevant cellular machine at the molecular level.
- Nour-el-Hana Abbassi
- , Marcin Jaciuk
- & Sebastian Glatt
-
Article
| Open AccessInterplay between Mg2+ and Ca2+ at multiple sites of the ryanodine receptor
Skeletal ryanodine receptor controls calcium mobilization indispensable for muscle contraction. Here, authors combine cryo-EM and molecular dynamics to uncover the structural basis of the intricate regulation of this channel by calcium and magnesium.
- Ashok R. Nayak
- , Warin Rangubpit
- & Montserrat Samsó
-
Article
| Open AccessIRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis
The endoplasmic reticulum (ER) is a major site of lipid peroxidation during ferroptosis. Here authors show that the ER protein IRE1α determines ferroptosis induction via regulating glutathione synthesis independent of the unfolded protein response.
- Dadi Jiang
- , Youming Guo
- & Albert C. Koong
-
Article
| Open AccessPost-translational modification-dependent oligomerization switch in regulation of global transcription and DNA damage repair during genotoxic stress
Here the authors show that the human transcription elongation factor AF9, part of Super Elongation Complex (SEC), undergoes oligomerization which can be reverted by post-translational modification in regulation of global transcription.
- Prathama Talukdar
- , Sujay Pal
- & Debabrata Biswas
-
Article
| Open AccessEnzyme-assisted high throughput sequencing of an expanded genetic alphabet at single base resolution
The expansion of the genetic code with synthetic nucleotides has broadened our ability to evolve DNA as a functional material, but we lack analytical tools for the expanded alphabet. Here the authors demonstrate an enzyme-assisted method for the sequencing of six-letter DNA.
- Bang Wang
- , Kevin M. Bradley
- & Steven A. Benner
-
Article
| Open AccessChemical manipulation of an activation/inhibition switch in the nuclear receptor PXR
PXR is a receptor activated by diverse compounds that triggers detoxification pathways in the cell, and blocking this receptor may increase the effectiveness of certain drugs. Here, the authors present the structural basis of PXR inhibition.
- Efren Garcia-Maldonado
- , Andrew D. Huber
- & Taosheng Chen
-
Article
| Open AccessDysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation
The impact of obesity on cancer remains insufficiently explored. Here the authors show that in mouse models, dysfunctional adipocytes exhibit low levels of BECN1 which induce YAP/TAZ activity to promote breast and colorectal tumor progression.
- Yaechan Song
- , Heeju Na
- & Han-Woong Lee
-
Article
| Open AccessAlpha-glucans from bacterial necromass indicate an intra-population loop within the marine carbon cycle
Phytoplankton blooms provoke bacterioplankton blooms, from which bacterial biomass (necromass) is released via zooplankton grazing and viral lysis. Here, Beidler et al. show that the bacterial biomass, including alpha-glucan polysaccharides generated from the consumption of algal organic matter, is reused by microbes in vitro and during a diatom-dominated bloom.
- Irena Beidler
- , Nicola Steinke
- & Thomas Schweder
-
Article
| Open AccessAnalysis of early intermediate states of the nitrogenase reaction by regularization of EPR spectra
Here, the authors characterize selenium and sulphur incorporated FeMo cofactors of the catalytic MoFe protein component from Azotobacter vinelandii under turnover conditions using EPR.
- Lorenz Heidinger
- , Kathryn Perez
- & Erik Schleicher
-
Article
| Open AccessOxidative photocatalysis on membranes triggers non-canonical pyroptosis
Oxidative damage to intracellular membrane proteins is critical to cells. Here, the authors use a water-oxidizing photocatalyst, generating ∙OH even under hypoxia, to show that membrane-specific protein oxidation triggers pyroptosis via non-canonical inflammasomes.
- Chaiheon Lee
- , Mingyu Park
- & Tae-Hyuk Kwon
-
Article
| Open AccessMicrofibril-associated glycoprotein 4 forms octamers that mediate interactions with elastogenic proteins and cells
Microfibrillar-associated protein 4 (MFAP4) is involved in fibrotic and cardiovascular diseases. Wozny et al. reveal structural aspects mediating MFAP4 octamer formation critical for its interaction with elastogenic proteins and cells.
- Michael R. Wozny
- , Valentin Nelea
- & Dieter P. Reinhardt
-
Article
| Open AccessStructural and dynamic insights into the activation of the μ-opioid receptor by an allosteric modulator
Here, the authors utilise NMR and cryo-EM to characterise the binding of an allosteric modulator to μ-opioid receptor (MOR), revealing modulator binding can potentiate receptor activation by altering the conformational dynamics in the core region of MOR.
- Shun Kaneko
- , Shunsuke Imai
- & Ichio Shimada
-
Article
| Open AccessDeep mutational scanning reveals a correlation between degradation and toxicity of thousands of aspartoacylase variants
The details of how the protein folding and degradation systems collaborate to combat potentially toxic non-native proteins are unknown. Here the authors perform systematic studies of missense and nonsense variants of the cytosolic aspartoacylase, ASPA, where loss-of-function variants are linked to Canavan disease.
- Martin Grønbæk-Thygesen
- , Vasileios Voutsinos
- & Rasmus Hartmann-Petersen
-
Article
| Open AccessTargeting bacterial nickel transport with aspergillomarasmine A suppresses virulence-associated Ni-dependent enzymes
Aspergillomarasmine A (AMA) chelates metal ions such as Zn2+ and Ni2+, which are essential for the activity of enzymes that are important for virulence of several pathogens. Here, Sychantha et al. show that AMA inhibits bacterial Ni2+ uptake and Ni-dependent enzymes, and reduces bacterial virulence in an animal infection model.
- David Sychantha
- , Xuefei Chen
- & Gerard D. Wright
-
Article
| Open AccessThe structural basis for 2′−5′/3′−5′-cGAMP synthesis by cGAS
Here, the authors provide structural and biochemical data describing the mechanism through which cGAS synthesizes 2′−5′/3′−5′-cGAMP.
- Shuai Wu
- , Sandra B. Gabelli
- & Jungsan Sohn
-
Article
| Open AccessStructural basis of human NOX5 activation
NADPH oxidase 5 (NOX5) is activated by Ca2+ signaling, catalyzing superoxide production by transferring electrons from intracellular NADPH to extracellular oxygen. Here the authors uncover the molecular basis of NOX5 activation and electron transfer.
- Chenxi Cui
- , Meiqin Jiang
- & Ji Sun
-
Article
| Open AccessStructural insights into drug transport by an aquaglyceroporin
Pentamidine and melarsoprol are drugs used to treat sleeping sickness caused by Trypanosoma brucei. Here, authors present cryo-EM structures of TbAQP2 with molecular dynamic simulations, revealing mechanisms shaping substrate specificity and drug permeation.
- Wanbiao Chen
- , Rongfeng Zou
- & Chongyuan Wang
-
Article
| Open AccessMutational dissection of a hole hopping route in a lytic polysaccharide monooxygenase (LPMO)
Lytic polysaccharide monooxygenases (LPMOs) are mono copper enzymes with outstanding industrial applicability. Here, the authors investigate the “hole hopping” mechanism in a bacterial LPMO and show that a strictly conserved tryptophan is critical for radical formation and hole transference, as well as reveal a correlation between the efficiency of hole transference and enzyme performance under oxidative stress.
- Iván Ayuso-Fernández
- , Tom Z. Emrich-Mills
- & Vincent G. H. Eijsink
-
Article
| Open AccessGenetic and functional diversity of β-N-acetylgalactosamine-targeting glycosidases expanded by deep-sea metagenome analysis
Four β-N-acetylgalactosaminidase gene families were identified via deep-sea metagenome analysis. The biochemical and structural characterization of the aforementioned enzymes revealed their functional diversity and monophyletic evolutionary history.
- Tomomi Sumida
- , Satoshi Hiraoka
- & Takuro Nunoura
-
Article
| Open AccessMultimodal binding and inhibition of bacterial ribosomes by the antimicrobial peptides Api137 and Api88
Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis. Here, the authors show that the honey-bee derived PrAMPs Api137 and Api88 inhibit bacterial ribosomes through multiple mechanisms, promising for drug development.
- Simon M. Lauer
- , Maren Reepmeyer
- & Ralf Hoffmann
-
Article
| Open AccessA nascent riboswitch helix orchestrates robust transcriptional regulation through signal integration
Here the authors unveil an intermediate state during the folding of the manganese riboswitch from L. lactis. This transient state allows the integration of multiple cellular signals including RNA polymerase pausing and transcription factor NusA.
- Adrien Chauvier
- , Shiba S. Dandpat
- & Nils G. Walter
-
Article
| Open AccessMolecular basis of bacterial DSR2 anti-phage defense and viral immune evasion
The defense-associated sirtuin 2 (DSR2) system protects bacteria from phages by depleting NAD+. Here, authors elucidate the molecular mechanisms underlying DSR2 assembly, activation, and inhibition, providing important insights into bacterial anti-phage defense.
- Jiafeng Huang
- , Keli Zhu
- & Ang Gao
-
Article
| Open AccessFragment ion intensity prediction improves the identification rate of non-tryptic peptides in timsTOF
Immunopeptidomics is crucial for the discovery of potential immunotherapy and vaccine candidates. Here, the authors generate a ground truth timsTOF dataset to fine-tune the deep learning model Prosit, improving peptide-spectrum match rescoring by up to 3-fold during immunopeptide identification.
- Charlotte Adams
- , Wassim Gabriel
- & Kurt Boonen
-
Article
| Open AccessUnveiling the A-to-I mRNA editing machinery and its regulation and evolution in fungi
A-to-I editing in animals is catalyzed by enzymes of the Adenosine Deaminase Acting on RNA family, orthologues of which do not exist in fungi. Here, Feng et al. characterise the enzymes involved in A-to-I mRNA editing in Fusarium graminearum.
- Chanjing Feng
- , Kaiyun Xin
- & Huiquan Liu
-
Article
| Open Access5′UTR G-quadruplex structure enhances translation in size dependent manner
In eukaryotes, G-quadruplex in mRNA (RG4) 5′ UTR inhibit translation initiation. Here the authors employ single molecule assay to show that RG4 in E. coli reporter increases translation efficiency by preventing ribosome dislodging.
- Chun-Ying Lee
- , Meera Joshi
- & Sua Myong
-
Article
| Open AccessOptimizing differential expression analysis for proteomics data via high-performing rules and ensemble inference
In proteomics, identifying differentially expressed proteins (DEPs) is critical for uncovering biomarkers and drug targets. However, constructing optimal workflows to achieve maximal identification of DEPs is challenging. Here, the authors performed 34,576 combinatorial experiments on 24 gold standard spike-in datasets to discern optimal workflows.
- Hui Peng
- , He Wang
- & Wilson Wen Bin Goh
-
Article
| Open AccessPrediction of m6A and m5C at single-molecule resolution reveals a transcriptome-wide co-occurrence of RNA modifications
The epitranscriptome holds many unexplored RNA functions, but detecting multiple modifications from one sample remains challenging. Here, authors devise a strategy combining AI and nanopore sequencing to uncover a transcriptome-wide co-occurrence of two modification types in individual RNA molecules.
- P Acera Mateos
- , A J Sethi
- & E Eyras
-
Article
| Open AccessInterplay of structural preorganization and conformational sampling in UDP-glucuronic acid 4-epimerase catalysis
Enzymes involve structural flexibility in their function, but understanding enzyme catalysis as connected to protein motions is a major challenge. Here, the authors obtain energetic description of C-H activation in nicotinamide coenzyme-dependent UDP-glucuronic acid C4 epimerase based on temperature kinetic studies and isotope effect measurements.
- Christian Rapp
- , Annika Borg
- & Bernd Nidetzky
-
Article
| Open AccessIntramolecular autoinhibition regulates the selectivity of PRPF40A tandem WW domains for proline-rich motifs
The specific recognition of a proline-rich motif in the intrinsically disordered region of SF1 by the PRPF40A tandem WW domains is modulated by an intramolecular autoinhibition, suggesting a general mechanism to enhance WW binding selectivity.
- Santiago Martínez-Lumbreras
- , Lena K. Träger
- & Michael Sattler
-
Article
| Open AccessIdentification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease
The LINE-1 retrotransposon is a target for the development of therapies to treat age-associated disease. Here the AUs describes the characterization of small molecule inhibitors of the endonuclease domain of LINE-1.
- Alexandra M. D’Ordine
- , Gerwald Jogl
- & John M. Sedivy
-
Article
| Open AccessCadmium binding by the F-box domain induces p97-mediated SCF complex disassembly to activate stress response programs
The F-box domain is a conserved structural motif in ubiquitin ligases known only to bind Skp1. Here, the authors show the F-box domain is also an environmental cadmium sensor that changes conformation upon binding to disassemble the active ligase, protecting the cell from cadmium stress.
- Linda Lauinger
- , Anna Andronicos
- & Peter Kaiser
-
Article
| Open AccessStructural basis and synergism of ATP and Na+ activation in bacterial K+ uptake system KtrAB
KtrAB complex is essential in K+ uptake for bacteria. Here authors illustrate the synergism of ATP and Na+ in activating K+ uptake of KtrAB from Bacillus subtilis and its gating mechanism, which may also shed light on other Na+-activated K+ channels.
- Wesley Tien Chiang
- , Yao-Kai Chang
- & Nien-Jen Hu
-
Article
| Open AccessMechanistic basis of the dynamic response of TWIK1 ionic selectivity to pH
Using computer simulations authors identify the dynamic molecular motions controlling the structural conformation of the TWIK1 ion channel, showing that its ability to transport sodium upon acidification result from the evolution of the classical potassium-selective pore.
- Franck C. Chatelain
- , Nicolas Gilbert
- & Olivier Bignucolo
-
Article
| Open AccessNative N-glycome profiling of single cells and ng-level blood isolates using label-free capillary electrophoresis-mass spectrometry
Single-cell manipulation and processing techniques and improvements in mass spectrometry sensitivity make single-cell proteomic profiling feasible. This study presents a label-free approach for the characterisation of native N-glycans of single mammalian cells and ng-level blood isolates, demonstrating the potential to detect cell surface glycome changes at the single-cell level in health or disease.
- Anne-Lise Marie
- , Yunfan Gao
- & Alexander R. Ivanov
-
Article
| Open AccessAn interphase actin wave promotes mitochondrial content mixing and organelle homeostasis
A mitochondrial actin wave fragments mitochondria. Here, the authors find that the wave produces force that is resisted by mitochondrial tethering, inducing fission, with subsequent fusion promoting mitochondrial content mixing and mitochondrial homeostasis.
- Stephen M. Coscia
- , Andrew S. Moore
- & Erika L. F. Holzbaur
-
Article
| Open AccessStructural basis for the intracellular regulation of ferritin degradation
Ferritin, the cellular iron storage complex, binds NCOA4 and is trafficked to the lysosome for degradation and iron release. Here, authors present the cryo-EM structure of the NCOA4-Ferritin complex with biophysical and cellular characterization.
- Fabian Hoelzgen
- , Thuy T. P. Nguyen
- & Gabriel A. Frank
-
Article
| Open AccessPharmacological inhibition of α-synuclein aggregation within liquid condensates
Aggregated forms of α-synuclein are characteristic of Parkinson’s disease. Here the authors show that the condensation-driven aggregation pathway of α-synuclein can be inhibited using small molecules: the aminosterol claramine stabilizes α-synuclein condensates and inhibits α-synuclein primary nucleation in the aggregation process.
- Samuel T. Dada
- , Zenon Toprakcioglu
- & Michele Vendruscolo
-
Article
| Open AccessSARS-CoV-2 Mpro responds to oxidation by forming disulfide and NOS/SONOS bonds
The main protease, a key enzyme of SARS-CoV-2, can protect itself from oxidative damage. Here, Reinke, Schubert, and colleagues used XFEL radiation to image the enzyme, revealing the disulfide and NOS/SONOS bonds that form in response to oxygen.
- Patrick Y. A. Reinke
- , Robin Schubert
- & Thomas J. Lane
Browse broader subjects
Browse narrower subjects
- Biocatalysis
- Biogeochemistry
- Bioinorganic chemistry
- Biophysical chemistry
- Carbohydrates
- Chemical modification
- Cytokines
- DNA
- Enzyme mechanisms
- Enzymes
- Glycobiology
- Glycomics
- Histocytochemistry
- Hormones
- Immunochemistry
- Ion channels
- Isoenzymes
- Kinases
- Lipidomics
- Lipids
- Metabolomics
- Metals
- Neurochemistry
- Peptides
- Prions
- Proteases
- Protein folding
- Proteins
- Proteolysis
- Proteomics
- RNA
- Structural biology