Featured
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| Open AccessIntegrating cryo-OrbiSIMS with computational modelling and metadynamics simulations enhances RNA structure prediction at atomic resolution
Conventional structural biology techniques are limited in deciphering complex RNA structures and dynamic interactions. Here the authors show an integrated approach that combines cryogenic OrbiSIMS (cryo-OrbiSIMS) with computational methods for modelling RNA structures at atomic resolution.
- Shannon Ward
- , Alex Childs
- & Aditi N. Borkar
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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
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Article
| Open AccessActive site remodeling in tumor-relevant IDH1 mutants drives distinct kinetic features and potential resistance mechanisms
Here the authors show mutants of isocitrate dehydrogenase 1 (IDH1), an enzyme implicated in various cancers, have distinct catalytic and structural features that drive their ability to generate an oncometabolite.
- Matthew Mealka
- , Nicole A. Sierra
- & Christal D. Sohl
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Article
| Open AccessThe complete assembly of human LAT1-4F2hc complex provides insights into its regulation, function and localisation
The amino acid transporter complex LAT1-4F2hc is considered a major drug target for many cancers. Here, the authors apply native mass spectrometry-based approaches to decode a complete LAT1-4F2hc assembly. To do this, they connect post-translational modification and endogenous phospholipid binding to super-dimerization, function and localisation of LAT1-4F2hc.
- Di Wu
- , Renhong Yan
- & Carol V. Robinson
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Article
| Open AccessDenaturing mass photometry for rapid optimization of chemical protein-protein cross-linking reactions
Choosing best chemical cross-linking (XL) reagents and conditions for studying protein-protein interactions in structural biology is laborious and lacks in accuracy. The authors develop here an accurate, fast, robust and quantiative denaturing mass photometry approach for screening of XL conditions.
- Hugo Gizardin-Fredon
- , Paulo E. Santo
- & Sarah Cianférani
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Article
| Open AccessTyrosine phosphorylation of CARM1 promotes its enzymatic activity and alters its target specificity
Coactivator-associated arginine methyltransferase 1 (CARM1) is an important target in hematologic malignancies. In this work, the authors show that the hyperactivation of Janus kinase 2 (JAK2) by the V617F mutation phosphorylates CARM1 which regulates its methyltransferase activity and alters its target specificity.
- Hidehiro Itonaga
- , Adnan K. Mookhtiar
- & Stephen D. Nimer
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Article
| Open AccessSelective lipid recruitment by an archaeal DPANN symbiont from its host
The symbiont Ca. Nanohaloarchaeum antarcticus is dependent on its host Halorubrum lacusprofundi for lipids due to a lack of certain biosynthetic genes. Here, the authors characterize the lipidome dynamics of this symbiotic relationship.
- Su Ding
- , Joshua N. Hamm
- & Anja Spang
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Article
| Open AccessCross-link assisted spatial proteomics to map sub-organelle proteomes and membrane protein topologies
The spatial mapping of proteins can give important functional insights. Here, Zhu et al. develop a cross-linking mass spectrometry-based spatial proteomics method that does not require protein engineering, affords sub-organelle resolution, and elucidates both protein locations and membrane topologies.
- Ying Zhu
- , Kerem Can Akkaya
- & Fan Liu
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Article
| Open AccessExposing the molecular heterogeneity of glycosylated biotherapeutics
The molecular heterogeneity of glycosylated biotherapeutics often complicates analysis by intact mass spectrometry. Here, the authors propose a simplified procedure for characterization that employs proton transfer charge reduction. Integration with glycomic and glycopeptide datasets can further provide glycoform-level information.
- Luis F. Schachner
- , Christopher Mullen
- & Wendy Sandoval
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Article
| Open AccessLDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments
The mechanisms transporting fatty acids into the cell are not completely understood. Here, the authors discover a selective transporter for a specific class of lipids, and show its role in regulating neutrophil function during myocardial ischemia-reperfusion injury.
- Wenwen Tang
- , Yi Luan
- & Dianqing Wu
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Article
| Open AccessSpiDe-Sr: blind super-resolution network for precise cell segmentation and clustering in spatial proteomics imaging
Imaging mass cytometry (IMC) is a powerful single-cell resolution platform for targeted spatial proteomics, but it can be constrained by imaging noise and resolution. Here, the authors propose SpiDe-Sr, a super-resolution network embedded with a denoising module for IMC spatial resolution enhancement.
- Rui Chen
- , Jiasu Xu
- & Xianting Ding
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Article
| Open AccessIon mobility-tandem mass spectrometry of mucin-type O-glycans
Currently, only a few specialized labs can characterize O-glycans. The present study couples high-resolution ion mobility spectrometry with tandem mass spectrometry to efficiently identify complex O-glycan structures in clinical samples.
- Leïla Bechtella
- , Jin Chunsheng
- & Kevin Pagel
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Article
| Open AccessThunder-DDA-PASEF enables high-coverage immunopeptidomics and is boosted by MS2Rescore with MS2PIP timsTOF fragmentation prediction model
Human leukocyte antigen (HLA) class I peptide ligands (HLAIps) are targets for developing vaccines and immunotherapies. Here the authors report Thunder-DDA-PASEF, an immunopeptidomics method which enhances the identification of vital HLAIps crucial for vaccine and immunotherapy development.
- David Gomez-Zepeda
- , Danielle Arnold-Schild
- & Stefan Tenzer
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Article
| Open AccessEfficient catalyst-free N2 fixation by water radical cations under ambient conditions
The growth and sustainable development of humanity is heavily dependent upon N2 fixation. Herein, authors developed an ambient catalyst-free disproportionation of N2 by water plasma to yield economically valuable nitroxyl and hydroxylamine products.
- Xiaoping Zhang
- , Rui Su
- & Huanwen Chen
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Article
| Open AccessMicropillar arrays, wide window acquisition and AI-based data analysis improve comprehensiveness in multiple proteomic applications
Obtaining a comprehensive proteomic profile for complex samples is still an elusive task. Here, the authors present an LC-MS/MS workflow including micropillar arrays, wide isolation windows and AI-based data analysis to boost proteomic coverage and throughput for multiple proteomic samples.
- Manuel Matzinger
- , Anna Schmücker
- & Rupert L. Mayer
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Article
| Open AccessMolecular-level architecture of Chlamydomonas reinhardtii’s glycoprotein-rich cell wall
Chlamydomonas reinhardtii produces a glycoprotein-rich cell wall. Using nuclear magnetic resonance and mass spectrometry approaches, this study reveals unprecedented details on its protein and carbohydrate content, and provide an atomic-level architecture model.
- Alexandre Poulhazan
- , Alexandre A. Arnold
- & Isabelle Marcotte
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Article
| Open AccessNanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping
Genetic association studies with affinity proteomics face challenges when dealing with protein altering variants. Suhre et al. show that nanoparticle enrichment mass-spectrometry can distinguish between epitope effects and bona fide protein quantitative traits.
- Karsten Suhre
- , Guhan Ram Venkataraman
- & Frank Schmidt
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Article
| Open AccessNuclear and cytoplasmic specific RNA binding proteome enrichment and its changes upon ferroptosis induction
The reported assay shows a subcellular-specific RNA labeling method for efficient enrichment and deep profiling of nuclear and cytoplasmic RBPs, the authors apply this to investigate changes of subcellular-specific RBP-RNA interactions in ferroptosis.
- Haofan Sun
- , Bin Fu
- & Weijie Qin
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Article
| Open AccessDeep learning-driven fragment ion series classification enables highly precise and sensitive de novo peptide sequencing
Accurate and high-throughput sequencing methods for proteins are lacking. Here the authors report Spectralis which improves de novo peptide sequencing using a convolutional layer that connects peaks in spectra spaced by amino acid masses, fragment ion series classification and a peptide-spectrum match confidence score.
- Daniela Klaproth-Andrade
- , Johannes Hingerl
- & Julien Gagneur
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Article
| Open AccessOpen access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics
Interpreting untargeted mass spectrometry (MS) data is challenging due to incomplete reference libraries. Here, the authors created the nearest neighbor suspect spectral library from largescale public MS data, significantly enhancing the ability to hypothesize structures for unknown mass spectra.
- Wout Bittremieux
- , Nicole E. Avalon
- & Pieter C. Dorrestein
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Article
| Open AccessSelenium-based metabolic oligosaccharide engineering strategy for quantitative glycan detection
Metabolic oligosaccharide engineering (MOE) is a classical strategy for carbohydrate perception but suffers from glycan quantification. Here the authors develop a selenium-based metabolic oligosaccharide engineering strategy (SeMOE), based on elemental analysis, to quantitatively detect and visualize glycans both in vitro and in vivo.
- Xiao Tian
- , Lingna Zheng
- & Ran Xie
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Article
| Open AccessDeepRTAlign: toward accurate retention time alignment for large cohort mass spectrometry data analysis
Retention time (RT) alignment is a crucial step in large cohort proteomics and metabolomics studies. Here, the authors introduce DeepRTAlign, a deep learning tool for RT alignment that shows high identification sensitivity and quantitative accuracy.
- Yi Liu
- , Yun Yang
- & Cheng Chang
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Article
| Open AccessDirect identification of interfacial degradation in blue OLEDs using nanoscale chemical depth profiling
Understanding the degradation mechanism of organic light-emitting diodes is essential to improve device performance and stability. Here, authors present a high-resolution diagnostic method to obtain molecular information with 7-nm depth resolution and analyse devices at different degradation levels.
- Gustavo F. Trindade
- , Soohwan Sul
- & Ian S. Gilmore
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Article
| Open AccessCommon origin of sterol biosynthesis points to a feeding strategy shift in Neoproterozoic animals
Sterane molecular fossils are used to compliment evidence from the fossil record. Here, the authors use a molecular clock to explore the origins of the smt gene, tracing the loss of sterol synthesis to dietary shifts in animals at the end-Neoproterozoic.
- T. Brunoir
- , C. Mulligan
- & D. A. Gold
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Article
| Open AccessImproved in situ characterization of protein complex dynamics at scale with thermal proximity co-aggregation
Vast majority of cellular activities are carried out by protein complexes that assembled dynamically in response to cellular needs and environmental cues. Here, the authors present Slim-TPCA, an effective and readily deployable strategy to unravel the functional roles of protein complexes en masse across various cellular processes.
- Siyuan Sun
- , Zhenxiang Zheng
- & Chris Soon Heng Tan
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Article
| Open AccessOn-tissue dataset-dependent MALDI-TIMS-MS2 bioimaging
There is a need for dataset-dependent MS2 acquisition in trapped ion mobility spectrometry imaging. Here the authors report spatial ion mobility-scheduled exhaustive fragmentation (SIMSEF) which enables on-tissue metabolite and lipid annotation in mass spectrometry bioimaging studies, and use this to visualise the chemical space in rat brains.
- Steffen Heuckeroth
- , Arne Behrens
- & Robin Schmid
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Article
| Open AccessStructural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans
In this work, the authors combine cryo-electron tomography of vitrified virions, mass spectrometry, modeling, molecular dynamics and infectivity assay and report that a hinge glycan on viral spike protein influences virus infection and immune evasion.
- David Chmielewski
- , Eric A. Wilson
- & Wah Chiu
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Article
| Open AccessDefining neutralization and allostery by antibodies against COVID-19 variants
Here, Tulsian et al. identified the effect of biologically relevant full-length IgG binding on the Spike protein from different SARS-CoV-2 variants to comprehensively understand the mechanisms of antibody evasion, towards the development of better antiviral strategies.
- Nikhil Kumar Tulsian
- , Raghuvamsi Venkata Palur
- & Paul Anthony MacAry
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Article
| Open AccessLocalized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease
The impact of antiparasitic treatment on local tissue responses in the case of chronic Chagas disease (caused by Trypanosoma cruzi infection) is not well understood. Authors provide insight into clinical treatment failure and drivers of post-infectious conditions.
- Zongyuan Liu
- , Rebecca Ulrich vonBargen
- & Laura-Isobel McCall
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Article
| Open AccessSialic acid O-acetylation patterns and glycosidic linkage type determination by ion mobility-mass spectrometry
O-acetylation is a common modification of sialic acids. Here, a library of synthetic O-acetylated sialosides made it possible to develop an ion mobility mass spectrometry (IM-MS) approach that can elucidate exact O-acetylation patterns and glycosidic linkage types of sialosides isolated from biological samples.
- Gaёl M. Vos
- , Kevin C. Hooijschuur
- & Geert-Jan Boons
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Article
| Open AccessPolyamine detergents tailored for native mass spectrometry studies of membrane proteins
Native mass spectrometry of membrane proteins in commonly used detergents are not ideal for preserving non-covalent interactions. Here, the authors develop new detergents for native MS of intact membrane proteins, opening new opportunities to study membrane proteins in various detergents.
- Yun Zhu
- , Bo-Ji Peng
- & Arthur Laganowsky
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Article
| Open AccessSingle-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging
Single-cell analysis provides unique insight into individual cell dynamics and cell-to-cell heterogeneity. Here, the authors utilize trapped ion mobility separation coupled with dual-polarity ionization mass spectrometry imaging to enable high-throughput in situ profiling of single-cell lipidome.
- Hua Zhang
- , Yuan Liu
- & Lingjun Li
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Article
| Open AccessAn integrated organoid omics map extends modeling potential of kidney disease
Lassé et al. show that genes involved in kidney organoid proteomic response to TNFα segregate a subset of individuals with poor outcomes in proteinuric kidney disease, demonstrating the relevance of kidney organoid modeling to human kidney disease.
- Moritz Lassé
- , Jamal El Saghir
- & Markus M. Rinschen
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Article
| Open AccessSimultaneously discovering the fate and biochemical effects of pharmaceuticals through untargeted metabolomics
Untargeted metabolomics enables simultaneous measurement of xenobiotic fate and effects in biological systems. This is demonstrated through discovering extensive biotransformation maps, measuring systemic exposures over time, and directly associating endogenous biochemical responses to internal dose.
- Tara J. Bowen
- , Andrew D. Southam
- & Mark R. Viant
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Article
| Open AccessConformational restriction shapes the inhibition of a multidrug efflux adaptor protein
Multidrug efflux protein pumps are key players in bacterial antimicrobial resistance. Here, the authors show how dynamics of a periplasmic pump component can be targeted for efflux inhibition.
- Benjamin Russell Lewis
- , Muhammad R. Uddin
- & Eamonn Reading
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Article
| Open AccessDeep-profiling of phospholipidome via rapid orthogonal separations and isomer-resolved mass spectrometry
The existence of large number of isomers poses challenges for lipidomic analysis. The authors integrate hydrophilic interaction liquid chromatography, trapped ion mobility, and isomer-resolved MS/MS into a single system, enabling deep profiling of phospholipidomes at fast speed and wide coverage.
- Tian Xia
- , Feng Zhou
- & Yu Xia
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Article
| Open AccessMass spectrometry imaging for biosolids characterization to assess ecological or health risks before reuse
Mass spectrometry imaging is a suitable tool for the analysis of non-cohesive materials. Here, authors show that it can be used to detect persistent organic pollutants (POPs) and heavy metals (HMs) in biosolids using small amounts of material with speed and safety.
- Claire Villette
- , Loïc Maurer
- & Dimitri Heintz
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Article
| Open AccessExpanded vacuum-stable gels for multiplexed high-resolution spatial histopathology
Emerging high-plex imaging technologies are limited in resolving subcellular biomolecular features. Here, the authors propose a spatial histopathology tool that allows for high-plex protein staining and physical expansion, while retaining the lateral tissue expansion.
- Yunhao Bai
- , Bokai Zhu
- & Sizun Jiang
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Article
| Open AccessOzone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome
Fatty acids are fundamental biomolecular building blocks that are characterized by extraordinary structural diversity and present a formidable analytical challenge. Here the authors introduce a discovery workflow for de novo identification that adds more than 100 fatty acids to the human lipidome.
- Jan Philipp Menzel
- , Reuben S. E. Young
- & Stephen J. Blanksby
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Article
| Open AccessUltra-fast and accurate electron ionization mass spectrum matching for compound identification with million-scale in-silico library
Accuracy loss and slow speed affect the identification of compounds through matching of mass spectra using a large-scale spectral library. Here the authors use Word2vec spectral embedding and hierarchical navigable small-world graph to improve accuracy and speed of spectral matching on their own million-scale in-silico library.
- Qiong Yang
- , Hongchao Ji
- & Zhimin Zhang
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Article
| Open AccessHybrid-DIA: intelligent data acquisition integrates targeted and discovery proteomics to analyze phospho-signaling in single spheroids
Standard mass spectrometry analyses often miss key targets required for phospho-signalling reconstruction. Here, authors present an intelligent data acquisition strategy that combines discovery and targeted analysis in one run and apply it to maximize the information from single spheroids drug screenings.
- Ana Martínez-Val
- , Kyle Fort
- & Jesper V. Olsen
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Article
| Open AccessData fusion and multivariate analysis for food authenticity analysis
Using two different mass spectrometric platforms, authors demonstrate how metabolomic data fusion and multivariate analysis can be used to accurately identify the geographic origin and production method of salmon.
- Yunhe Hong
- , Nicholas Birse
- & Christopher T. Elliott
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Article
| Open AccessThe UBX domain in UBXD1 organizes ubiquitin binding at the C-terminus of the VCP/p97 AAA-ATPase
The function of VCP/p97 AAA-ATPase cofactor UBXD1 and its UBX domain has been elusive. Here the authors show that the extended UBXD1 UBX domain is located at the p97 pore exit where it binds ubiquitin, suggesting that UBXD1 receives unfolded substrates and hands them off for down-stream processing.
- Mike Blueggel
- , Alexander Kroening
- & Christine Beuck
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Article
| Open AccessSerine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling
In the DNA damage response, ADP-ribosylation is an essential signaling pathway. Here the authors utilize a multidisciplinary approach to establish its molecular basis in fruit flies and provide evidence for Drosophila’s suitability as model organism.
- Pietro Fontana
- , Sara C. Buch-Larsen
- & Ivan Ahel
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Article
| Open AccessStructural insights into perilipin 3 membrane association in response to diacylglycerol accumulation
Perilipin 3 binds to emerging lipid droplets from the endoplasmic reticulum. Choi and Ajjaji et al characterize the molecular mechanisms of Perilipin 3 recruitment to membranes and uncover a function for the PAT domain in diacylglycerol sensing.
- Yong Mi Choi
- , Dalila Ajjaji
- & Michael V. Airola
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Article
| Open AccessAllosteric regulation of the 20S proteasome by the Catalytic Core Regulators (CCRs) family
A family of regulators named Catalytic Core Regulators (CCRs) oversees the function of the 20S proteasome. Here, the authors show that CCRs function through an allosteric mechanism, coupling the physical binding of the PSMB4 β-subunit with attenuation of the proteasome three proteolytic activities.
- Fanindra Kumar Deshmukh
- , Gili Ben-Nissan
- & Michal Sharon
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Article
| Open AccessDetermining the gas-phase structures of α-helical peptides from shape, microsolvation, and intramolecular distance data
It remains challenging to gauge the gas-phase structure of biomolecular ions and assess to what extent native-like structures are maintained. Here, the authors utilize Förster resonance energy transfer and ion mobility spectrometry for more stringent structural characterization of biomolecular ions.
- Ri Wu
- , Jonas B. Metternich
- & Renato Zenobi
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Article
| Open AccessUsing mass spectrometry imaging to map fluxes quantitatively in the tumor ecosystem
Isotopologue spectral analysis was originally designed to assess metabolic fluxes from bulk samples. Here, the authors adapted this approach to infer fluxes from discrete regions in tissue by using mass spectrometry imaging, showing increased fatty acid synthesis flux in brain tumors of mice.
- Michaela Schwaiger-Haber
- , Ethan Stancliffe
- & Gary J. Patti
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Article
| Open AccessElucidating the molecular programming of a nonlinear non-ribosomal peptide synthetase responsible for fungal siderophore biosynthesis
Fungal siderophores are biosynthesised by nonribosomal peptide synthetases (NRPSs) with highly unusual domain architectures. Here, the authors characterise cryptic programming events occurring within SidC NRPS, responsible for ferricrocin biosynthesis in Aspergillus nidulans.
- Matthew Jenner
- , Yang Hai
- & Yi Tang