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Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development
Cell metabolism has emerged as a major factor implicated in human brain evolution. Here, the authors show that an ape-specific enzyme enhances the ability of a human-specific enzyme to increase glutaminolysis and therefore expand the size of the human neocortex.
- Lei Xing
- , Vasiliki Gkini
- & Takashi Namba
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Article
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F-actin architecture determines the conversion of chemical energy into mechanical work
F-actin architecture modulates transmission and generation of stresses in cells, yet its impact on myosin ATP hydrolysis remains unknown. The authors perform experiments measuring myosin ATP hydrolysis rates, showing that F-actin architecture can control myosin energy consumption.
- Ryota Sakamoto
- & Michael P. Murrell
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Article
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Temporal coordination of the transcription factor response to H2O2 stress
H2O2 stress is known to activate a slew of transcription factors that restore redox balance. Here, the authors use live-cell imaging and single-cell analysis to reveal that the transcription factors that are activated and their timing of activation is dose dependent.
- Elizabeth Jose
- , Woody March-Steinman
- & Andrew L. Paek
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Structural and biochemical analysis of family 92 carbohydrate-binding modules uncovers multivalent binding to β-glucans
Carbohydrate binding modules (CBMs) are non-catalytic domains found within multi-modular carbohydrate-active enzymes like glycoside hydrolases. Here, the authors show the crystal structures of two CBM family 92 members, which use three different surface binding sites to bind to β-glucans.
- Meng-Shu Hao
- , Scott Mazurkewich
- & Lauren S. McKee
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Article
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Tyrosine 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
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Structural insights into the transporting and catalyzing mechanism of DltB in LTA D-alanylation
Here, the authors structurally and functionally characterise DltB, a member of the Membrane-Bound O-AcylTransferase (MBOAT) superfamily responsible for D-alanine incorporation in the cell wall of gram-positive bacteria.
- Pingfeng Zhang
- & Zheng Liu
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Article
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RNA targeting and cleavage by the type III-Dv CRISPR effector complex
Here, Schwartz, Bravo, and Ahsan et al. show how multi-subunit fusion proteins are arranged around a crRNA in a type III CRISPR-Cas effector to cleave target RNA. Structures and molecular dynamics of this complex show three distinct active sites that can be used for programmable RNA cleavage.
- Evan A. Schwartz
- , Jack P. K. Bravo
- & David W. Taylor
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Mechanoelectronic stimulation of autologous extracellular vesicle biosynthesis implant for gut microbiota modulation
Pathogenic gut microbiota is responsible for a few debilitating gastrointestinal Diseases. Here, the authors develop a wireless mechanoelectronic device designed to manufacture of functional vesicles in vivo to regulate microbiome.
- Shuangshuang Wan
- , Kepeng Wang
- & Lianhui Wang
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Article
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Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila
Mitochondrial fission, performed by Drp1, is carefully regulated, particularly in neurons. Here, the authors examine Drosophila Cdk8/CDK19 function in mitochondrial fission and uncover a role phosphorylating Drp1 in the cytoplasm and show overexpression suppresses a Parkinson’s disease model.
- Jenny Zhe Liao
- , Hyung-lok Chung
- & Esther M. Verheyen
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Article
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Local environment in biomolecular condensates modulates enzymatic activity across length scales
Here, the authors show that biomolecular condensates can enhance enzymatic rates by creating distinct solvent environments compared to the surrounding solution, and this emergent property can manifest within assemblies as small as nanometers.
- Marcos Gil-Garcia
- , Ana I. Benítez-Mateos
- & Paolo Arosio
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Article
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Modulation of peroxisomal import by the PEX13 SH3 domain and a proximal FxxxF binding motif
Import of proteins into peroxisomes depends on PEX5, PEX13 and PEX14. Here the authors obtain crystal structures and NMR data to show the recognition of diaromatic peptide motifs on a noncanonical surface of the PEX13 SH3 domain, revealing a dynamic network which modulates peroxisomal matrix import.
- Stefan Gaussmann
- , Rebecca Peschel
- & Michael Sattler
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Article
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The genetic landscape of a metabolic interaction
Reynolds and colleagues examine a biochemically-mediated epistatic interaction between metabolic enzymes involved in folate metabolism and show that biochemical coupling shapes the range of enzyme activities sufficient to rescue cell growth.
- Thuy N. Nguyen
- , Christine Ingle
- & Kimberly A. Reynolds
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Article
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Rapid evolutionary change in trait correlations of single proteins
Trait correlations impact evolvability as selection on one trait can influence others. Here, the authors examine trait correlation in two proteins, a fluorescent protein & an antibiotic resistance enzyme, observing rapid evolution of trait correlations through changes in the biophysical properties of these proteins.
- Pouria Dasmeh
- , Jia Zheng
- & Andreas Wagner
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Article
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Cross-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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An enzymatic continuous-flow reactor based on a pore-size matching nano- and isoporous block copolymer membrane
Continuous-flow biocatalysis with immobilized enzymes is a sustainable route for chemical synthesis, but inadequate biocatalytic efficiency caused by non-productive enzyme immobilization or enzyme-carrier mismatches presents a challenge for its application. Here, the authors report an approach for the fabrication of a high-performance enzymatic continuous-flow reactor via integrating scalable isoporous block copolymer membranes as carriers with an oriented one-step enzyme immobilization via a genetically fused material binding peptide.
- Zhenzhen Zhang
- , Liang Gao
- & Volker Abetz
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Article
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MmcA is an electron conduit that facilitates both intracellular and extracellular electron transport in Methanosarcina acetivorans
Methanogens conserve energy through methane generation, however the biochemical details of anaerobic respiration in methanogens remain unclear. Here, authors show a multiheme c-type cytochrome, MmcA, plays a critical role in methanogenesis and anaerobic respiration.
- Dinesh Gupta
- , Keying Chen
- & Dipti D. Nayak
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Article
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The DEAD-box ATPase Dbp10/DDX54 initiates peptidyl transferase center formation during 60S ribosome biogenesis
Cruz et al. describe the role of Dbp10/DDX54 in remodeling rRNA structure within the immature eukaryotic peptidyl transferase center of the ribosome, coupling energy-dependent catalysis to a post-catalytic role in factor exchange during 60S ribosomal subunit assembly.
- Victor E. Cruz
- , Christine S. Weirich
- & Jan P. Erzberger
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Mechanism and structural dynamics of sulfur transfer during de novo [2Fe-2S] cluster assembly on ISCU2
The biogenesis of iron-sulfur proteins in eukaryotes is initiated by the mitochondrial core ISC complex. Here, the authors provide structural, biochemical and spectroscopic data to characterize sulfur transfer intermediates in the core ISC complex.
- Vinzent Schulz
- , Ralf Steinhilper
- & Roland Lill
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Exposing 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
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ATP-free in vitro biotransformation of starch-derived maltodextrin into poly-3-hydroxybutyrate via acetyl-CoA
Several in vitro synthetic enzymatic biosystems (ivSEBs) to produce poly-3-hydroxybutyrate (PHB) via acetyl-coenzyme A (acetyl-CoA) have been reported, but suffer from complicated operation procedures, low yields, and/or dependence on costly ATP. Here, the authors report the design of an ATP-free ivSEB for one-pot, high-yield PHB biosynthesis via acetyl-CoA utilizing starch-derived maltodextrin as the sole substrate.
- Xinlei Wei
- , Xue Yang
- & Chun You
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Article
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Insights into the inhibition of protospacer integration via direct interaction between Cas2 and AcrVA5
Here, the authors characterize an anti-CRISPR protein that prevents protospacer integration by Cas1-Cas2, providing structural insights that may benefit CRISPR-Cas systems research.
- Mingfang Bi
- , Wenjing Su
- & Xiaobing Mo
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Article
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Cryo-EM structures of adenosine receptor A3AR bound to selective agonists
Adenosine A3 receptor (A3AR) holds promise for treating inflammatory and cancer conditions. Here, Cai et al. present cryo-EM structures of A3AR bound to agonists CF101 and CF102, offering insights into its activation and ligand interaction, crucial for developing targeted therapies.
- Hongmin Cai
- , Shimeng Guo
- & H. Eric Xu
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Article
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Tertiary structure and conformational dynamics of the anti-amyloidogenic chaperone DNAJB6b at atomistic resolution
Adupa et al show how the anti-amyloidogenic molecular chaperone DNAJB6 adopts three conformational states that determine the accessibility of its substrate binding domain. In all states, interactions with HSP70 are shielded, suggesting that functional interactions only may occur upon substrate binding.
- Vasista Adupa
- , Elizaveta Ustyantseva
- & Patrick R. Onck
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Article
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Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase
Here the authors present the cryo-EM structure of active and inhibited human MTHFR, revealing a dynamic inhibitory mechanism dependent on dual SAM binding. The resulting closed conformation features an autoinhibitory element effectively blocking enzymatic activity.
- Linnea K. M. Blomgren
- , Melanie Huber
- & Thomas J. McCorvie
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Article
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Sm-like protein Rof inhibits transcription termination factor ρ by binding site obstruction and conformational insulation
Said et al. used cryoEM, biochemistry and bioinformatics to uncover how the Sm-like protein Rof regulates transcription termination. Rof binds termination factor ρ, inhibiting ρ ring closure and its association with RNA or transcription complexes.
- Nelly Said
- , Mark Finazzo
- & Markus C. Wahl
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Article
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KdpD is a tandem serine histidine kinase that controls K+ pump KdpFABC transcriptionally and post-translationally
KdpD is known as the sensory histidine kinase of two-component system KdpDE that controls the transcription of the kdpFABC genes. Here, the authors show that KdpD acts as atypical serine kinase, which post-translationally regulates KdpFABC.
- Jakob M. Silberberg
- , Sophie Ketter
- & Inga Hänelt
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Remote loop evolution reveals a complex biological function for chitinase enzymes beyond the active site
Loop regions play a key role in protein evolution. Herein the authors demonstrate how GH19 chitinase acquired additional antifungal activity by introducing remote loops, without compromising its original function. This work offers an innovative approach to expand enzyme function.
- Dan Kozome
- , Adnan Sljoka
- & Paola Laurino
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Article
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A widely conserved protein Rof inhibits transcription termination factor Rho and promotes Salmonella virulence program
Bacterial protein Rof (Rho-off) directly interacts with bacterial factor Rho and inhibits Rho-dependent transcription termination. Here, authors report cryo-EM structure of Rho-Rof antitermination complex and reveal their role in bacterial pathogenesis.
- Jing Zhang
- , Shuo Zhang
- & Chengyuan Wang
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Article
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One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse
With structural models now available on a proteome scale, Malatesta et al. show that structure-based screening can help identify proteins catalyzing orphan reactions in metabolic pathways, offering functional insights beyond sequence-based approaches.
- Marco Malatesta
- , Emanuele Fornasier
- & Riccardo Percudani
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Comment
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All-inclusive nitrifiers in Antarctic soils
Multidisciplinary culture-dependent and -independent techniques elucidate the unique microbial nitrogen cycle in nutrient-poor coastal Antarctica soils and reveal the contribution of novel key microbes to their nitrogen budget.
- Maximiliano Ortiz
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Article
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A hemoprotein with a zinc-mirror heme site ties heme availability to carbon metabolism in cyanobacteria
Heme is an abundant cofactor required by nearly all known organisms. Here, authors discover a cyanobacterial protein with a distinct Zn-mirror heme site, which may function to sense heme and regulate energy metabolism.
- Nicolas Grosjean
- , Estella F. Yee
- & Crysten E. Blaby-Haas
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Article
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A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules
De novo fermentation and synthetic pathway construction for halogen-containing molecules remain relatively underexplored. Here, the authors report a mix-and-match co-culture platform to de novo generate a large array of halogenated tryptophan derivatives in E. coli from glucose.
- Kevin B. Reed
- , Sierra M. Brooks
- & Hal S. Alper
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Article
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Reciprocating RNA Polymerase batters through roadblocks
During transcription, RNA polymerases may encounter protein roadblocks along template DNA. Here, Qian et al. use magnetic tweezers to show that RNA polymerases can backtrack and ram into longer lived roadblocks to transit through them.
- Jin Qian
- , Allison Cartee
- & Laura Finzi
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Article
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Regulation by the RNA-binding protein Unkempt at its effector interface
How RNA-binding proteins (RBPs) regulate gene expression via effectors of RNA processing is unclear. Here, the authors dissect the effector interface of an essential RBP, Unkempt, and investigate its contribution to translational control in cells.
- Kriti Shah
- , Shiyang He
- & Jernej Murn
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Article
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Protein disulfide isomerase cleaves allosteric disulfides in histidine-rich glycoprotein to regulate thrombosis
Vascular protein disulfide isomerase (PDI) regulates thrombosis and targeting extracellular PDI remains a promising antithrombotic approach. Here, the authors show that PDI cleaves allosteric disulfides on histidine-rich glycoprotein to influence its functions during coagulation and thus fine-tune the kinetics of thrombus formation.
- Keyu Lv
- , Shuai Chen
- & Chao Fang
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Tension activation of mechanosensitive two-pore domain K+ channels TRAAK, TREK-1, and TREK-2
TRAAK, TREK-1 and TREK-2 are mechanosensitive potassium channels involved in action potential propagation among other roles. Here, authors quantify their tension response and show ultrasound can generate tension to activate ion channels.
- Ben Sorum
- , Trevor Docter
- & Stephen G. Brohawn
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Article
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Nardilysin-regulated scission mechanism activates polo-like kinase 3 to suppress the development of pancreatic cancer
Polo-like kinase 3 (Plk3) has a tumor suppressive role through the induction of apoptosis, however, the mechanism underlying its activation is unclear. Here, in pancreatic cancer, the authors show that activation of Plk3 is dependent on its cleavage into p41Plk3, by the metalloendopeptidase nardilysin.
- Jie Fu
- , Jianhua Ling
- & Paul J. Chiao
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Fuzzy recognition by the prokaryotic transcription factor HigA2 from Vibrio cholerae
Here, the authors dissect the fuzzy interaction between the prokaryote transcription factor HigA2 and its DNA target and show that specific, transient interactions drive specificity despite HigA2 remaining mostly disordered.
- San Hadži
- , Zala Živič
- & Remy Loris
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Article
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A subgroup of light-driven sodium pumps with an additional Schiff base counterion
Light-driven sodium-pumping rhodopsins are unique ion transporters. Here, authors present a characterization of such rhodopsins with a modified active center allowing for efficient sodium transport under various environmental conditions.
- E. Podoliak
- , G. H. U. Lamm
- & K. Kovalev
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Article
| Open Access
Integrated proteomics reveals autophagy landscape and an autophagy receptor controlling PKA-RI complex homeostasis in neurons
The health of brain cells is known to depend on functional autophagy, but the details are unclear. Here, the authors perform systematic proteomic profiling of human and mouse neurons, delineating the landscape of autophagy degradation in brain.
- Xiaoting Zhou
- , You-Kyung Lee
- & Zhenyu Yue
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Article
| Open Access
Electrochemically coupled CH4 and CO2 consumption driven by microbial processes
The microbial valorisation of greenhouse gases could offer promising approaches climate change mitigation. Here, authors demonstrate the coupling of methane oxidation and carbon dioxide reduction by microbial consortia, facilitated by the redox cycling of iron minerals.
- Yue Zheng
- , Huan Wang
- & Feng Zhao
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Article
| Open Access
Antigen-specific Fab profiling achieves molecular-resolution analysis of human autoantibody repertoires in rheumatoid arthritis
Although many autoimmune diseases are characterized by the presence of autoantibodies, complete characterisation of autoantibody repertoires is lacking. Here, the authors introduce an autoantigen-specific Fab profiling method to show that the autoantibody repertoire in rheumatoid arthritis is diverse yet dominated only by a few clones.
- Eva Maria Stork
- , Danique M. H. van Rijswijck
- & Albert Bondt
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Article
| Open Access
A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell
Ligand discovery against membrane proteins has been a major challenge, mainly due to the peculiar nature of their natural habitat. Here, the authors designed a new chemical proteomic probe that targets the lysines exposed on the cell surface and developed a chemical proteomic strategy for global analysis of surface functionality in living cells.
- Ting Wang
- , Shiyun Ma
- & Haojie Lu
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Article
| Open Access
The assembly platform FimD is required to obtain the most stable quaternary structure of type 1 pili
Type 1 pili are crucial cell surface bacterial virulence factors. Here, the authors show that FimD is required to assemble the most stable quaternary pilus structure by ensuring that the resulting protein polymer is free of structural defects.
- Dawid S. Zyla
- , Thomas Wiegand
- & Rudi Glockshuber
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Article
| Open Access
Cryo-EM structure of the human Asc-1 transporter complex
The human Asc-1-4F2hc complex plays an important role in the neural development and stability. Here, authors determine the cryo-EM structures of Asc-1-4F2hc complex in three states, revealing its substrate recognition and transport mechanism.
- Yaning Li
- , Yingying Guo
- & Renhong Yan
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Article
| Open Access
Engineering an artificial catch bond using mechanical anisotropy
Catch bonds are unique protein-protein interactions where the bond lifetime increases under external pulling forces. Here, the authors engineer an artificial catch bond based on a non-catch bonding human gut bacterial adhesion protein complex.
- Zhaowei Liu
- , Haipei Liu
- & Michael A. Nash
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Article
| Open Access
Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter
Asc1/CD98hc is a key regulator of small neutral amino acid transport in the brain and adipose tissue. Here, authors report the structure of semi-occluded hAsc1/CD98hc and provide a model for Asc1 exchange and facilitated diffusion modes of transport.
- Josep Rullo-Tubau
- , Maria Martinez-Molledo
- & Oscar Llorca
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Article
| Open Access
Probing altered receptor specificities of antigenically drifting human H3N2 viruses by chemoenzymatic synthesis, NMR, and modeling
Binding modes of antigenically drifted hemagglutinins of human influenza A viruses have been determined by NMR using synthetic N-glycans having 13C-labeled monosaccharides to pinpoint which monosaccharides of extended LacNAc chains engage with the HAs.
- Luca Unione
- , Augustinus N. A. Ammerlaan
- & Geert-Jan Boons
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Article
| Open Access
Chemical unclonable functions based on operable random DNA pools
Physical unclonable functions provide algorithm-independent cryptography based on non-distributable unique tokens. Here, the authors introduce unclonable functions based on random DNA pools, enabling secure decentralized authentication.
- Anne M. Luescher
- , Andreas L. Gimpel
- & Robert N. Grass
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