Featured
-
-
Article
| Open AccessStructural basis for calcium-stimulating pore formation of Vibrio α-hemolysin
Vibrio α-hemolysins (αHLs) are toxins crucial for certain bacterial infections. Here the authors reveal that calcium ions boost the activity of a specific toxin, Vibrio campbellii αHL, and uncover its calcium-dependent activation mechanism.
- Yu-Chuan Chiu
- , Min-Chi Yeh
- & Shih-Ming Lin
-
Article
| Open AccessStructural insights into FSP1 catalysis and ferroptosis inhibition
FSP1 suppress ferroptosis by reducing CoQ10, yet the underlying mechanism how FSP1 reduces CoQ remains unknown. Here, the authors reveal that the homodimerization of FSP1 via its unique CTD is required for the catalytic activity and ferroptosis suppression and provide insight potentially useful to drug design.
- Yun Lv
- , Chunhui Liang
- & Deyu Zhu
-
Article
| Open AccessIdentification and characterization of endo-α-, exo-α-, and exo-β-d-arabinofuranosidases degrading lipoarabinomannan and arabinogalactan of mycobacteria
Lipoarabinomannan and arabinogalactan in the mycobacterial cell wall contain d-arabinan core. Here, the authors identify and characterize the molecular structures and mechanisms of four bacterial enzymes that synergistically degrade the alpha- and beta-linkages of d-arabinan.
- Michiko Shimokawa
- , Akihiro Ishiwata
- & Kiyotaka Fujita
-
Article
| Open AccessMolecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase
NGTs glycosylate asparagine residues in proteins, crucial for bacterial adhesion and pathogenicity. Here, the authors provide insights via crystallography and simulations, showing acceptor asparagine uses imidic form for catalysis and UDP-glucose phosphate group acts as general base.
- Beatriz Piniello
- , Javier Macías-León
- & Ramon Hurtado-Guerrero
-
Article
| Open AccessStructural insights into functional properties of the oxidized form of cytochrome c oxidase
Using resonance Raman spectroscopy and serial femtosecond X-ray crystallography, the authors show the heme a3 iron and CuB in the resting oxidized form of Cytochrome c Oxidase are coordinated by a hydroxide ion and a water molecule, respectively.
- Izumi Ishigami
- , Raymond G. Sierra
- & Denis L. Rousseau
-
Article
| Open AccessThe structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family
Although the precise function of Tryptophan rich antigen multi-gene family (TRAgs) proteins is not known in any Plasmodium species several members of the P. vivax TRAg family have been reported to have red blood cell binding properties. Here, Kundu and Naskar et al. provide the X-ray crystallography structure of a P. vivax TRAg domain of PVP01_0000100. Structural and biochemical assays suggest a lipid binding function for a pan-Plasmodium multi-gene family.
- Prasun Kundu
- , Deboki Naskar
- & Julian C. Rayner
-
Article
| Open AccessClass III hybrid cluster protein homodimeric architecture shows evolutionary relationship with Ni, Fe-carbon monoxide dehydrogenases
Here, the authors present an X-ray crystal structure of a class III hybrid cluster protein (HCP), structurally similar to Ni, Fe-carbon monoxide dehydrogenases (CODHs), enabling conclusions to be drawn regarding the structural evolution of HCP/CODH superfamily.
- Takashi Fujishiro
- & Kyosei Takaoka
-
Article
| Open AccessMultifunctional human monoclonal antibody combination mediates protection against Rift Valley fever virus at low doses
There are currently no treatment options for infection with Rift Valley fever virus (RVFV). Here, Chapman et al., show that a combination of human monoclonal antibodies targeting two different steps in early virus cell entry enhances protection in a mouse model and is effective at low doses.
- Nathaniel S. Chapman
- , Ruben J. G. Hulswit
- & James E. Crowe Jr.
-
Article
| Open AccessThe H163A mutation unravels an oxidized conformation of the SARS-CoV-2 main protease
SARS-CoV-2 main protease adapts a disulfide bonded inactive state to escape oxidative stress. Here, the authors report a crystal structure of an inactive conformation of the enzyme achieved through a H163A mutation, and the mechanistic details of conformational changes using atomistic simulations.
- Norman Tran
- , Sathish Dasari
- & Aravindhan Ganesan
-
Article
| Open AccessMultidisciplinary studies with mutated HIV-1 capsid proteins reveal structural mechanisms of lattice stabilization
The effects of E45A or P38A capsid mutations on HIV core stability and infectivity are reversed by R132T or T216I. Here, authors used structural and biophysical methods to reveal short- and long-range rearrangements that explain stability changes.
- Anna T. Gres
- , Karen A. Kirby
- & Stefan G. Sarafianos
-
Article
| Open AccessHeterogeneity in M. tuberculosis β-lactamase inhibition by Sulbactam
Here, the reaction of the suicide inhibitor sulbactam with the M. tuberculosis β-lactamase (BlaC) is investigated with time-resolved crystallography. Singular Value Decomposition is implemented to extract kinetic information despite changes in unit cell parameters during the time-course of the reaction.
- Tek Narsingh Malla
- , Kara Zielinski
- & Marius Schmidt
-
Article
| Open AccessO-methyltransferase-like enzyme catalyzed diazo installation in polyketide biosynthesis
Diazo compounds, such as kinamycin, are rare bioactive natural products whose assembly has been extensively studied, but the formation of the diazo group is elusive. Here, the authors report O-methyltransferase-like protein, AlpH, which is responsible for the l-glutamylhydrazine incorporation in kinamycin biosynthesis.
- Yuchun Zhao
- , Xiangyang Liu
- & Ming Jiang
-
Article
| Open AccessStructure-based design of a strain transcending AMA1-RON2L malaria vaccine
Here the authors use structure-based design to engineer a single component immunogen that mimics the malaria parasite AMA1-RON2 complex required for invasion of host cells, and show that it elicits a potent strain-transcending antibody response in rats.
- Palak N. Patel
- , Thayne H. Dickey
- & Niraj H. Tolia
-
Article
| Open AccessStructural basis of lipid-droplet localization of 17-beta-hydroxysteroid dehydrogenase 13
Hydroxysteroid 17-beta-dehydrogenase 13 (HSD17B13) is a hepatic lipid droplet-associated enzyme that is upregulated in patients with non-alcoholic fatty liver disease. Here, the authors report crystal structures of HSD17B13 and its complexes with two series of inhibitors.
- Shenping Liu
- , Ruth F. Sommese
- & Michelle F. Clasquin
-
Article
| Open AccessCrystal structure and functional implications of cyclic di-pyrimidine-synthesizing cGAS/DncV-like nucleotidyltransferases
Here, the authors present structural and functional characterization of bacterial CD-NTases that synthesize cyclic dipyrimidines for phage resistance, revealing a (R/Q)xW motif dictating pyrimidine selection which suggests a sequential pathway for synthesizing 2’3’-cyclic di-UMP.
- Chia-Shin Yang
- , Tzu-Ping Ko
- & Yeh Chen
-
Article
| Open AccessCharacterization of two O-methyltransferases involved in the biosynthesis of O-methylated catechins in tea plant
Tea contains catechins such as (−)-epigallocatechin gallate (EGCG) which have antioxidant activity and potential health benefits. Here the authors characterise two enzymes that produce O-methylated EGCG, a modified form found in some tea cultivars that has improved bioavailability.
- Ji-Qiang Jin
- , Fu-Rong Qu
- & Liang Chen
-
Article
| Open AccessHydrophobic interactions dominate the recognition of a KRAS G12V neoantigen
Mutation associated neoantigens are a family of highly specific therapeutic targets for the treatment of cancer. Here, the authors describe the cryo-EM structure of an antibody bound to a neoantigen complex providing insights into the specificity of the antibody.
- Katharine M. Wright
- , Sarah R. DiNapoli
- & Sandra B. Gabelli
-
Article
| Open AccessRedox driven B12-ligand switch drives CarH photoresponse
CarH is a bacterial B12-binding photoreceptor involved in transcriptional regulation. Here, the authors provide insights into B12 dynamics and associated cobalt redox changes following light activation. These demonstrate the CarH response integrates light and oxygen sensing.
- Harshwardhan Poddar
- , Ronald Rios-Santacruz
- & David Leys
-
Article
| Open AccessCD98hc is a target for brain delivery of biotherapeutics
New delivery platforms are needed to allow broader application of biotherapeutics for CNS diseases. Here, the authors show enhanced CNS delivery with a transport vehicle engineered to bind CD98hc, a highly expressed target at the blood-brain barrier.
- Kylie S. Chew
- , Robert C. Wells
- & Mihalis S. Kariolis
-
Article
| Open AccessCrystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing
The unusual crystal structures of MHC I-peptide complexes provide a visualization of the remarkable ability of the groove to adapt conformationally to bound peptides, explaining how MHC I molecules edit peptides in antigen presentation.
- Lenong Li
- , Xubiao Peng
- & Marlene Bouvier
-
Article
| Open AccessMenT nucleotidyltransferase toxins extend tRNA acceptor stems and can be inhibited by asymmetrical antitoxin binding
Bacteria can control their growth using internal toxins regulated by antitoxins. Here, the authors show MenT toxins from Mycobacterium tuberculosis work by modifying tRNAs, and asymmetric antitoxin binding blocks toxin activity.
- Xibing Xu
- , Ben Usher
- & Pierre Genevaux
-
Article
| Open AccessHigh resolution cryo-EM and crystallographic snapshots of the actinobacterial two-in-one 2-oxoglutarate dehydrogenase
The 2-oxoglutarate dehydrogenase complex (ODH) is a textbook example of multienzymatic machinery. Here, the authors report the structural and regulatory properties of the Actinobacterial enzyme OdhA, a fusion of two ODH components acting in a supercomplex with pyruvate dehydrogenase.
- Lu Yang
- , Tristan Wagner
- & Marco Bellinzoni
-
Article
| Open AccessMechanism of U6 snRNA oligouridylation by human TUT1
U6 snRNA plays a catalytic role in pre-mRNA splicing. Here the authors report the structure of human terminal uridyltransferase, TUT1, complexed with U6 snRNA revealing the mechanism of specific uridylation of U6 snRNA by TUT1.
- Seisuke Yamashita
- & Kozo Tomita
-
Article
| Open AccessCatalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase
Vibrio dual lipases/transferases are virulence-related enzymes, with both substrate and catalytic promiscuity. Wang et al reveal their prominent structural flexibility, proposing a catalytic site tuning mechanism underlying enzyme promiscuity.
- Chongyang Wang
- , Changshui Liu
- & Qingjun Ma
-
Article
| Open AccessStructure of lasso peptide epimerase MslH reveals metal-dependent acid/base catalytic mechanism
MslH, encoded in the MS-271 biosynthetic gene cluster, catalyzes the epimerization at the Cα center of the MslA C-terminal Trp21, however, the detailed catalytic process was unknown. Here, the authors report MslH is a metallo-dependent peptide epimerase with a calcineurin-like fold.
- Yu Nakashima
- , Atsushi Kawakami
- & Hiroyuki Morita
-
Article
| Open AccessBtuB TonB-dependent transporters and BtuG surface lipoproteins form stable complexes for vitamin B12 uptake in gut Bacteroides
Uptake of vitamin B12 is important for colonisation of the gut by Bacteroides species. Here the authors characterise B12 uptake in Bacteroides thetaiotaomicron, mediated by outer membrane protein complexes consisting of surface-exposed BtuG lipoproteins and BtuB TonB-dependent transporters.
- Javier Abellon-Ruiz
- , Kalyanashis Jana
- & Bert van den Berg
-
Article
| Open AccessMolecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome
The mechanism by which the chromatinized HBV genome is transcribed remains poorly understood. In this study, Liu et al. demonstrate how HBx exploits Spindlin1, a histone methylation reader, to overcome heterochromatin barriers and enhance HBV transcription from the cccDNA minichromosome.
- Wei Liu
- , Qiyan Yao
- & Haitao Li
-
Article
| Open AccessMolecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome
Here the authors use fast kinetics, X-ray crystallography, and cryo-EM to uncover the mechanism of ribosome inhibition by amikacin and kanamycin. They find that amikacin binds near the P-site tRNA, offering new strategies to fight antibiotic resistance.
- Savannah M. Seely
- , Narayan P. Parajuli
- & Matthieu G. Gagnon
-
Article
| Open AccessPolymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formation
In this work, the authors highlight that conserved receptor binding segments of class B GPCR ligands have a dual nature: they serve as amyloid-prone regions involved in pH-dependent conversion from secretory amyloid fibrils to the functional folded form.
- Dániel Horváth
- , Zsolt Dürvanger
- & András Perczel
-
Article
| Open AccessDiscovery and rational engineering of PET hydrolase with both mesophilic and thermophilic PET hydrolase properties
Extensive research efforts have been directed towards the development of PET hydrolases with improved activity, but template enzymes used are limited. Here, the authors report a PET hydrolase from Cryptosporangium aurantiacum (CaPETase) that exhibits high thermostability and PET degradation activity at ambient temperatures and determine its crystal structure.
- Hwaseok Hong
- , Dongwoo Ki
- & Kyung-Jin Kim
-
Article
| Open AccessZinc-finger BED domains drive the formation of the active Hermes transpososome by asymmetric DNA binding
Hermes is a member of the eukaryotic hAT DNA transposon superfamily. Its transposase forms a ring-shaped tetramer of dimers to provide sufficient number of DNA binding BED domains to locate its transposon left-end in genomic DNA and facilitate the subsequent interaction with the right-end.
- Laurie Lannes
- , Christopher M. Furman
- & Fred Dyda
-
Article
| Open AccessRAD51C-XRCC3 structure and cancer patient mutations define DNA replication roles
In this study, the authors present structures and functional analyses for the RAD51C-XRCC3 tumor suppressor complex, providing insights into recurrent mutations in cancer and Fanconi Anemia patients that uncover distinct DNA replication fork protection, restart and reversal regions.
- Michael A. Longo
- , Sunetra Roy
- & Katharina Schlacher
-
Article
| Open AccessCrystal structures of herbicide-detoxifying esterase reveal a lid loop affecting substrate binding and activity
The esterase SulE, which detoxifies and hydrolyses a variety of sulfonylurea herbicides, is increasingly of interest in efforts to eliminate environmental contamination of sulfonylurea herbicides and engineer herbicide-tolerant crops. Here, the SulE is structurally and mechanistically characterised.
- Bin Liu
- , Weiwu Wang
- & Jian He
-
Article
| Open AccessArchitecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair
B12-dependent human methylmalonly-CoA mutase (MMUT) requires the chaperone MMAA. The authors report the crystal structure of MMUT-MMAA, which shows a MMAA-driven conformational change in MMUT involved n B12 loading and repair and helps explain the effects of disease-causing MMAA-MMUT interface mutations.
- Romila Mascarenhas
- , Markus Ruetz
- & Ruma Banerjee
-
Article
| Open AccessStructures of p53/BCL-2 complex suggest a mechanism for p53 to antagonize BCL-2 activity
The human tumor suppressor p53 interacts with the BCL-2 family proteins to regulate apoptosis. Here, the authors solve the structures of p53 in complex with the antiapoptotic protein BCL-2 and suggest a mechanism by which p53 promotes apoptosis by competitively antagonizing the interaction of BCL-2 with pro-apoptotic BCL-2 family proteins.
- Hudie Wei
- , Haolan Wang
- & Yongheng Chen
-
Article
| Open AccessStructural basis for specific RNA recognition by the alternative splicing factor RBM5
The RNA binding protein RBM5 regulates alternative splicing of genes implicated in cancer. Here the authors show structural mechanisms how multiple RNA binding domains of RBM5 cooperate to recognize specific target RNA sequences.
- Komal Soni
- , Pravin Kumar Ankush Jagtap
- & Michael Sattler
-
Article
| Open AccessThe structural basis of divalent cation block in a tetrameric prokaryotic sodium channel
Divalent cation block is observed in various tetrameric ion channels. Here, authors use X-ray crystallography, electrophysiology and molecular dynamics simulations to reveal the mechanism of the divalent cation block on a prokaryotic sodium channel.
- Katsumasa Irie
- , Yoshinori Oda
- & Yoshinori Fujiyoshi
-
Article
| Open AccessEngineering broad-spectrum inhibitors of inflammatory chemokines from subclass A3 tick evasins
Tick evasin proteins block the inflammatory activity of mammalian chemokines. In this work, the authors report that structure-based modification of class A3 evasins alters their chemokine selectivity, suggesting these evasins could be engineered for targeted anti-inflammatory therapy.
- Shankar Raj Devkota
- , Pramod Aryal
- & Martin J. Stone
-
Article
| Open AccessStructural insights into the mechanism of overcoming Erm-mediated resistance by macrolides acting together with hygromycin-A
The authors discovered that hygromycin A not only enhances the cell-killing properties of macrolides but also renders them active against resistant bacteria. The provided structures of antibiotic pairs in complex with WT and macrolide-resistant ribosomes rationalize binding cooperativity of these drugs.
- Chih-Wei Chen
- , Nadja Leimer
- & Maxim S. Svetlov
-
Article
| Open AccessCytochrome c lysine acetylation regulates cellular respiration and cell death in ischemic skeletal muscle
The authors report that acetylation of cytochrome c on K39 acts as a molecular switch in ischemic skeletal muscle, but not other tissues, to increase respiration and prevent apoptosis. This gives skeletal muscle robust resilience to ischemia and ischemia-reperfusion injury.
- Paul T. Morse
- , Gonzalo Pérez-Mejías
- & Maik Hüttemann
-
Article
| Open AccessStructural journey of an insecticidal protein against western corn rootworm
The insecticidal protein Mpf2Ba1 shows potent control against corn rootworm. Here, the authors present detailed structural analyses revealing transitions between its three main stages of pore formation. These findings uncover molecular mechanisms of bacterial pore assembly and advance both crop biotechnology and food security.
- Guendalina Marini
- , Brad Poland
- & Helen R. Saibil
-
Article
| Open AccessAtomic structure of a nudivirus occlusion body protein determined from a 70-year-old crystal sample
Viral occlusion bodies are robust protein crystals that encapsulate virions of some insect viruses. Here, the authors determine the nudivirus occlusion body structure and describe common principles of occlusion body structure.
- Jeremy R. Keown
- , Adam D. Crawshaw
- & Jonathan M. Grimes
-
Article
| Open AccessStructural and photophysical characterization of the small ultra-red fluorescent protein
Researchers determined the three-dimensional structure of the small Ultra-Red Fluorescent Protein (smURFP) to understand its properties and the previous directed evolution process. In addition, they show smURFP fluoresces longer than small molecules.
- Atanu Maiti
- , Cosmo Z. Buffalo
- & Erik A. Rodriguez
-
Article
| Open AccessStructures of a FtsZ single protofilament and a double-helical tube in complex with a monobody
The cryoEM structures of a single protofilament of FtsZ from Klebsiella pneumoniae (KpFtsZ) in a polymerization-preferred conformation are presented and of a double-helical tube of the FtsZ–monobody complex that shows two parallel protofilaments.
- Junso Fujita
- , Hiroshi Amesaka
- & Hiroyoshi Matsumura
-
Article
| Open AccessThe structural pathology for hypophosphatasia caused by malfunctional tissue non-specific alkaline phosphatase
Hypophosphatasia (HPP) is a bone disease caused by mutations in tissue non-specific alkaline phosphatase (TNAP). Here, authors solved the crystal and cryoEM structures of TNAP, shedding light on the molecular mechanisms underlying HPP.
- Yating Yu
- , Kewei Rong
- & An Qin
-
Article
| Open AccessMolecular insights into the catalytic promiscuity of a bacterial diterpene synthase
Diterpene synthase VenA catalyses the synthesis of venezuelaene A with a unique 5-5-6-7 tetracyclic skeleton from geranylgeranyl pyrophosphate. Here, the authors report crystal structures of apo- and holo-VenA, provide mechanistic insights into its substrate selectivity and promiscuity, and engineer VenA into a sesterterpene synthase.
- Zhong Li
- , Lilan Zhang
- & Shengying Li
-
Article
| Open AccessIdentification of the SARS-unique domain of SARS-CoV-2 as an antiviral target
The SARS-unique domain (SUD) of SARS-CoV-2 plays important roles in virus life cycle. Here the authors determine the crystal structure of SARS-CoV-2 SUD and perform a compound screen, which identify theaflavin 3,3’-digallate as a potent SUD binder that exhibits anti-SARS-CoV-2 activity.
- Bo Qin
- , Ziheng Li
- & Sheng Cui
-
Article
| Open AccessMolecular mechanism of phosphopeptide neoantigen immunogenicity
Phosphorylated peptide antigens are present on cancer cells, but their role in cancer immunity is unknown. Here, the authors describe a molecular mechanism, by which a tumor-specific phosphopeptide found in acute myeloid leukemia is recognized by the human immune T cells.
- Yury Patskovsky
- , Aswin Natarajan
- & Michelle Krogsgaard
-
Article
| Open AccessStructural basis of the interaction between BCL9-Pygo and LDB-SSBP complexes in assembling the Wnt enhanceosome
The Wnt enhanceosome is responsible for the transactivation of Wnt target genes in response to stimulation of cells by extracellular Wnt signals. Here, Wang et al. show BCL9, Pygo, LDB1 and SSBP form a stable core complex within the Wnt enhanceosome. Furthermore, they determine the crystal structure of the Pygo2-LDB1-SSBP2 ternary complex, which provides a promising therapeutic target for blocking Wnt/β-catenin signaling in cancer.
- Hongyang Wang
- , Mariann Bienz
- & Wenqing Xu