Featured
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Article
| Open AccessImpact of secretin receptor homo-dimerization on natural ligand binding
GPCRs can form functionally important dimers. Here, authors study impact of dimerization of the secretin receptor on peptide ligand binding and show high receptor conformational dynamics that facilitate G protein recruitment and activation.
- Kaleeckal G. Harikumar
- , Sarah J. Piper
- & Laurence J. Miller
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Article
| Open AccessAngle between DNA linker and nucleosome core particle regulates array compaction revealed by individual-particle cryo-electron tomography
Here, using cryo-ET, the 3D structures of individual nucleosome particles were characterized to observe changes under varying ionic strengths and in the presence of protein H1, revealing key regulatory roles in chromatin organization dynamics.
- Meng Zhang
- , César Díaz-Celis
- & Gang Ren
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Article
| Open AccessDevelopment of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus
Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating widely in birds and have recently caused large outbreaks in mammals. Here, Furey et al. develop a clade 2.3.4.4b HA-expressing mRNA-LNP vaccine and show that it elicits strong protective immune responses in mice and ferrets.
- Colleen Furey
- , Gabrielle Scher
- & Scott E. Hensley
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Article
| Open AccessCystine-knot peptide inhibitors of HTRA1 bind to a cryptic pocket within the active site region
Here the authors use phage display to develop cystine-knot peptides that inhibit the trimeric serine protease HTRA1. Structural and biochemical characterisation uncovered binding of the peptides to a cryptic pocket that locked the active site in a noncompetent state.
- Yanjie Li
- , Yuehua Wei
- & Daniel Kirchhofer
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Article
| 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 AccessActive transcription and epigenetic reactions synergistically regulate meso-scale genomic organization
Chromatin within interphase nuclei forms compacted nanoscale DNA domains of uniform size. By integrating theory and imaging, here the authors show how the interplay between transcription and epigenetic mechanisms determine this size, independent of cell type.
- Aayush Kant
- , Zixian Guo
- & Vivek B. Shenoy
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Article
| Open AccessCellular structure of dinosaur scales reveals retention of reptile-type skin during the evolutionary transition to feathers
The evolution of feathers is associated with the evolution of related skin microstructures. Here, the authors demonstrate that Psittacosaurus, a non-avian feathered dinosaur, retained scaled skin like its ancestors in body regions lacking feathers.
- Zixiao Yang
- , Baoyu Jiang
- & Maria E. McNamara
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Article
| Open AccessThe actin cytoskeleton plays multiple roles in structural colour formation in butterfly wing scales
NCOMMS-23-44446C Vivid structural colours in butterflies are caused by photonic nanostructures scattering light, however insight into the development of such structures in vivo remains scarce. Here the authors show that actin plays a vital and direct templating role during structural colour formation in butterfly scales, providing ridge patterning mechanisms that are likely universal across lepidoptera.
- Victoria J. Lloyd
- , Stephanie L. Burg
- & Andrew J. Parnell
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Article
| Open AccessCopper(I)-nitrene platform for chemoproteomic profiling of methionine
Methionine plays an essential role in various biological and cell regulatory processes, making its chemoproteomic profiling necessary to understand its function. Here, the authors present Copper(I)-Nitrene Platform (CuNiP) for robust and selective labelling of methionine to generate highly stable sulfonyl sulfimide conjugates under physiological conditions.
- Samrat Sahu
- , Benjamin Emenike
- & Monika Raj
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Article
| Open AccessInvariant γδTCR natural killer-like effector T cells in the naked mole-rat
Naked mole-rats are long-lived rodents known to be resistant to the development of cancer, yet their immune system remains poorly explored. Here, the authors identify natural killer-like effector γδ T cells that express a dominant γδ T cell receptor and may serve a role in tumour immunosurveillance.
- Guillem Sanchez Sanchez
- , Stephan Emmrich
- & David Vermijlen
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Article
| Open AccessPhotoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN) for cross-modal individual analysis of the whole brain
Here, the authors introduce Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN) - a high-speed, non-destructive photoacoustic brain imaging technique that constructs 3D fluorescent maps of the brain and improves upon some of the limitations associated with traditional whole-brain optical imaging techniques.
- Yuwen Chen
- , Haoyu Yang
- & Bo Lei
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Article
| Open AccessLong-term relapse-free survival enabled by integrating targeted antibacteria in antitumor treatment
Tumor-resident intracellular microbiota (TRIM) could be a potential target for anticancer treatment. Here the authors report Au@Ag2Se nano-assemblies enabling bacterial killing, tumor inhibition and immune regulation in tumor microenvironment.
- Yuanlin Wang
- , Yaqian Han
- & Miao Yu
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Article
| Open AccessThe matrisome landscape controlling in vivo germ cell fates
The developmental fate of cells is regulated by the delicate environment created by the extracellular matrix. Here, authors investigate the impact of the full complement of conserved matrisome genes in germ cell development and gamete health in C. elegans.
- Aqilah Amran
- , Lara Pigatto
- & Sandeep Gopal
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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
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Article
| Open AccessHigh-throughput mechanical phenotyping and transcriptomics of single cells
The molecular system regulating cell surface mechanics remains largely unexplored at single-cell resolution. Here, the authors report a high-throughput single-cell assay, ELASTomics, which integrates mechanical phenotyping with unbiased transcriptomics.
- Akifumi Shiomi
- , Taikopaul Kaneko
- & Hirofumi Shintaku
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Article
| Open AccessStructural mechanisms for binding and activation of a contact-quenched fluorophore by RhoBAST
FLAPs have recently emerged as RNA counterparts to fluorescent proteins. Here, the authors determine the crystal structure of a FLAP called RhoBAST in complex with its ligand TMR-DN and reveal the mechanisms for binding and activation.
- Yufan Zhang
- , Zhonghe Xu
- & Xianyang Fang
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Article
| Open AccessZero-shot learning enables instant denoising and super-resolution in optical fluorescence microscopy
The authors introduce ZS-DeconvNet, an unsupervised computational super-resolution method for multiple types of microscopes, that enhances image resolution by more than 1.5 times over the diffraction limit with 10 times lower fluorescence than regular superresolution imaging conditions.
- Chang Qiao
- , Yunmin Zeng
- & Qionghai Dai
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Article
| Open AccessCorrelative single molecule lattice light sheet imaging reveals the dynamic relationship between nucleosomes and the local chromatin environment
This study combines lattice light sheet microscopy and single molecule imaging to study protein dynamics and chromatin structure in live cells. The authors describe how nucleosomes and proteins move and are organised in relation to chromatin density.
- Timothy A. Daugird
- , Yu Shi
- & Wesley R. Legant
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Article
| Open AccessMolecular fingerprinting of biological nanoparticles with a label-free optofluidic platform
Biosensing tools to detect multiple analytes in a high-throughput manner are still hindered by many limitations. Here, the authors present a label-free optofluidic platform integrating digital holography and microfluidics for analyte detection, allowing for the fingerprinting of heterogenous biological samples.
- Alexia Stollmann
- , Jose Garcia-Guirado
- & Romain Quidant
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Article
| Open AccessHepatocytes differentiate into intestinal epithelial cells through a hybrid epithelial/mesenchymal cell state in culture
Hepatocytes dedifferentiate into progenitor-like cells in culture. Here, authors elucidate the dynamics and mechanisms of hepatocyte dedifferentiation and find an unexpected differentiation potential of hepatocytes into intestinal epithelial cells.
- Shizuka Miura
- , Kenichi Horisawa
- & Atsushi Suzuki
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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
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Article
| Open AccessDynamin1 long- and short-tail isoforms exploit distinct recruitment and spatial patterns to form endocytic nanoclusters
Dynamins are required at nascent endosomes to promote membrane fission. Here, the authors use super-resolution microscopy to show that dynamin-1 recruitment relies on pre-existing nanoclusters and trapping of molecules laterally diffusing on the plasma membrane.
- Anmin Jiang
- , Kye Kudo
- & Frédéric A. Meunier
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Article
| Open AccessProteome partitioning constraints in long-term laboratory evolution
Adaptive laboratory evolution provides a real-time record of physiological change. In bacteria adapted to glucose over 40 000 generations, this study finds an apparent increase in enzyme efficiency consistent with increased substrate saturation due to loss of a flux sensing mechanism early in adaptation.
- Matteo Mori
- , Vadim Patsalo
- & Matthew Scott
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Article
| Open AccessThree-dimensional liquid metal-based neuro-interfaces for human hippocampal organoids
Providing a suitable multi-electrode array (MEA) for free-floating neural organoids is a great challenge. Here, authors present a mesh soft stretchable MEA for recording neural signals in human hippocampal organoids derived from induced pluripotent stem cells.
- Yan Wu
- , Jinhao Cheng
- & Xingyu Jiang
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Article
| Open AccessGene editing for latent herpes simplex virus infection reduces viral load and shedding in vivo
The main challenge for anti-HSV therapy is to target latent virus in ganglionic neurons. Here, the authors report a well-tolerated anti-HSV gene editing approach against HSV which targets latent HSV genomes and leads to reductions of ganglionic viral loads, and viral shedding upon reactivation in mouse models.
- Martine Aubert
- , Anoria K. Haick
- & Keith R. Jerome
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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
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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
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Article
| Open AccessA cell-free nutrient-supplemented perfusate allows four-day ex vivo metabolic preservation of human kidneys
As demand for organ transplants exceeds availability there has been an unmet need to extend preservation of deceased donor kidneys. Here, the authors show that a cell-free nutrient-supplemented perfusate allows 4-day preservation of human kidneys using spatially resolved lipidomics and metabolomics.
- Marlon J. A. de Haan
- , Marleen E. Jacobs
- & Ton J. Rabelink
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Article
| Open AccessSpatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity
Hepatocytes are central for maintaining metabolic homeostasis during nutritional transitions. Here, we show that the structural remodelling of hepatic organelles is part of hepatocytes’ metabolic plasticity to adapt to cycles of fasting/feeding and this process is zonated in the liver.
- Güneş Parlakgül
- , Song Pang
- & Ana Paula Arruda
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Article
| Open AccessComprehensive assessment of mRNA isoform detection methods for long-read sequencing data
Recently, various computational tools have emerged for detecting mRNA isoforms using long-read sequencing data. Here, the authors systemically evaluate and compare the performance of these tools.
- Yaqi Su
- , Zhejian Yu
- & Wanlu Liu
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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 AccessMultiplexed bulk and single-cell RNA-seq hybrid enables cost-efficient disease modeling with chimeric organoids
IPSC-derived organoids model diseases. Multiplexed coculture and demultiplexing natural genetic barcodes aid in studying genetic effects. Here, authors introduce Vireo-bulk to deconvolve bulk RNA-seq data, quantify donor abundance and identify differentially expressed genes.
- Chen Cheng
- , Gang Wang
- & Jin Zhang
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Matters Arising
| Open AccessReply to: Technical challenges of studying the impact of plasma components on the efficacy of lipid nanoparticles for vaccine and therapeutic applications
- Kai Liu
- , Elisa Lázaro-Ibáñez
- & Alan Sabirsh
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Article
| Open AccessA genetically encoded biosensor to monitor dynamic changes of c-di-GMP with high temporal resolution
The ubiquitous second messenger c-di-GMP regulates many biological processes in bacteria, including cell cycle, motility, virulence and biofilm formation. Here, Kaczmarczyk et al. develop a c-di-GMP biosensor that enables dynamic real-time tracking of c-di-GMP levels in individual living cells.
- Andreas Kaczmarczyk
- , Simon van Vliet
- & Urs Jenal
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Article
| Open AccessARTseq-FISH reveals position-dependent differences in gene expression of micropatterned mESCs
Hu et al. describe ARTseq-FISH, a spatial omics method that enables multiplexed detection of mRNAs, proteins and phospho-proteins simultaneously and at the same resolution. The authors investigate gene expression changes in a heterogenous colony of micropatterned mESCs.
- Xinyu Hu
- , Bob van Sluijs
- & Maike M. K. Hansen
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Article
| Open AccessChiral coordination polymer nanowires boost radiation-induced in situ tumor vaccination
Radiation-induced tumor vaccination is insufficient to elicit robust antitumor immune response. Here they combine chiral vidarabine monophosphate-gadolinium nanowires with immune checkpoint blockade therapy to synergistically induce antitumor immunity.
Reviewer recognition:
- Zhusheng Huang
- , Rong Gu
- & Ahu Yuan
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Article
| Open AccessThe Shigella kinase effector OspG modulates host ubiquitin signaling to escape septin-cage entrapment
Here, Xian et al. use phosphoproteomics to identify that the Shigella effector OspG interacts with a regulator of Cullin-RING ubiquitin ligases to promote the ubiquitination of septins and consequent inhibition of septin cage formation.
- Wei Xian
- , Jiaqi Fu
- & Xiaoyun Liu
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Article
| Open AccessIdentification of a family of species-selective complex I inhibitors as potential anthelmintics
Soil-transmitted helminths (STHs) are major pathogens. Here the authors screen 480 structural families of natural products to find compounds that kill Caenorhabditis elegans specifically when they require rhodoquinone (RQ)-dependent metabolism: they identify several classes of compounds and show some compounds kill adult STHs.
- Taylor Davie
- , Xènia Serrat
- & Andrew G. Fraser
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Article
| Open AccessMetabolic phenotyping reveals an emerging role of ammonia abnormality in Alzheimer’s disease
Metabolic implications in AD are unclear. Here, authors found significant correlations between cognitive impairment and metabolic features in a Chinese aging cohort (n = 1397). The study highlights ammonia disturbance as a potential therapeutic target for AD.
- Tianlu Chen
- , Fengfeng Pan
- & Wei Jia
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Article
| Open AccessHarnessing noncanonical crRNA for highly efficient genome editing
The inclusion of base Z has the potential to heighten the binding affinity between complementary nucleic acids. Here, the authors integrated base Z into CRISRP-Cas12a crRNA to augment the interaction between the crRNA and the target DNA, resulting in a significant enhancement of editing efficiency.
- Guanhua Xun
- , Zhixin Zhu
- & Huimin Zhao
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Article
| Open AccessCRISPR-dCas13d-based deep screening of proximal and distal splicing-regulatory elements
Here the authors develop Splice-RUSH, a high-throughput screening method to map both proximal and distal splicing-regulatory sequences in a native sequence context. These sequences can also be targeted by ASOs to modulate splicing.
- Yocelyn Recinos
- , Dmytro Ustianenko
- & Chaolin Zhang
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Article
| Open AccessThe miR-144/Hmgn2 regulatory axis orchestrates chromatin organization during erythropoiesis
Differentiation of stem and progenitor cells is a highly regulated process. Here, the authors uncover miR-144 and its target Hmgn2 as the backbone of the genetic regulatory circuit that controls the terminal differentiation of erythrocytes in vertebrates.
- Dmitry A. Kretov
- , Leighton Folkes
- & Daniel Cifuentes
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Article
| Open AccessIn vivo genome editing via CRISPR/Cas9-mediated homology-independent targeted integration for Bietti crystalline corneoretinal dystrophy treatment
Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive chorioretinal degenerative disease without approved therapeutic drug. Here, the authors show a promising CRISPR/Cas9 mediated homology-independent targeted integration therapy in patient derived cells and humanized mice carrying BCD mutations.
- Xiang Meng
- , Ruixuan Jia
- & Liping Yang
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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 AccessAn adeno-associated virus variant enabling efficient ocular-directed gene delivery across species
In non-human primates, rAAVs are delivered through suprachoroidal injection at a high dose to achieve optimal efficacy. Here, the authors present a novel AAV capsid (AAVv128) that significantly improved the transduction efficiency in photoreceptor and retinal pigment epithelial cells across species.
- Shuang Luo
- , Hao Jiang
- & Xun Sun
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Article
| Open AccessGiant organelle vesicles to uncover intracellular membrane mechanics and plasticity
The biophysical properties of cellular organelles are difficult to study directly. Here, the authors generate and characterize osmotically-expanded giant vesicles of several organelles, which maintain some of their functional properties.
- Alexandre Santinho
- , Maxime Carpentier
- & Abdou Rachid Thiam
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Article
| Open AccessA statistical resolution measure of fluorescence microscopy with finite photons
Abbe’s diffraction limit has been a defining concept for microscopy. With finite photon, photon noise remains one essential factor yet to be considered in the theoretical resolution limit. Here, the authors introduced information-based resolution limit allowing for photon-considered resolution assessment of various microscopy and super-resolution modalities.
- Yilun Li
- & Fang Huang
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Article
| Open AccessSynthetic intrinsically disordered protein fusion tags that enhance protein solubility
Insoluble protein expression continues to be a bottleneck for biotechnology. Here, Chilkoti and colleagues report a method for generating and identifying hypersoluble intrinsically disordered protein fusion tags to improve soluble protein expression and rescue protein function.
- Nicholas C. Tang
- , Jonathan C. Su
- & Ashutosh Chilkoti
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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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