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| Open AccessThe structural basis for the phospholipid remodeling by lysophosphatidylcholine acyltransferase 3
During phosphatidylcholine (PC) remodeling re-acylation is catalyzed by lysophosphatidylcholine acyltransferases (LPCAT). Here, the authors present crystal and cryo-EM structures of chicken LPCAT3 in the apo-, acyl donor-bound and acyl receptor-bound states, and based on the structures and further functional analysis they discuss the mechanism of the enzyme.
- Qing Zhang
- , Deqiang Yao
- & Yu Cao
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Article
| Open AccessArchitecture of the outer-membrane core complex from a conjugative type IV secretion system
DNA transfer between two bacterial cells is mediated by the conjugative type 4 secretion systems (T4SSs). Here, the authors report the structure of a complete T4SS outer-membrane core complex (OMCC), revealing distinct C17 and C13 symmetries of its central inner and peripheral outer ring regions, respectively.
- Himani Amin
- , Aravindan Ilangovan
- & Tiago R. D. Costa
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Article
| Open AccessN-terminal tyrosine of ISCU2 triggers [2Fe-2S] cluster synthesis by ISCU2 dimerization
[2Fe-2S] protein cofactors are essential for life and are synthesized on ISCU2 scaffolds. Here, the authors show that hydrophobic interaction of two conserved N-terminal tyrosines induces ISCU2 dimerization and concomitant [2Fe-2S] cluster synthesis.
- Sven-A. Freibert
- , Michal T. Boniecki
- & Roland Lill
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Article
| Open AccessCryo-EM structures of intermediates suggest an alternative catalytic reaction cycle for cytochrome c oxidase
Cytochrome c oxidase is a fundamental enzyme of life and its mechanism is not fully understood yet. Here, the authors present four cryo-EM structures of different intermediate states, which suggest an alternative cytochrome c oxidase reaction cycle.
- F. Kolbe
- , S. Safarian
- & H. Michel
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Article
| Open AccessStructure of the class C orphan GPCR GPR158 in complex with RGS7-Gβ5
The orphan GPR158 receptor belongs to the class C GPCR family and interacts with the regulator of G protein signaling 7 (RGS7)-Gβ5 complex. Here, the authors present the cryo-EM structure of human GPR158, which reveals that the extracellular domain contains a PAS domain, and they also determine the structures of GPR158 in complex with either one or two RGS7-Gβ5 heterodimers and discuss implications for the signaling mechanism.
- Eunyoung Jeong
- , Yoojoong Kim
- & Yunje Cho
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Article
| Open AccessHuman RIPK3 maintains MLKL in an inactive conformation prior to cell death by necroptosis
The pseudokinase MLKL is activated by the upstream kinase RIPK3 in the necroptotic pathway but the structural basis of MLKL activation is not well understood yet. Here, the authors present the crystal structures of the human RIPK3:MLKL complex and human RIPK3 kinase alone, which reveal structural differences between human and murine RIPK3 and they discuss mechanistic implications.
- Yanxiang Meng
- , Katherine A. Davies
- & James M. Murphy
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Article
| Open AccessPhosphorylation activates the yeast small heat shock protein Hsp26 by weakening domain contacts in the oligomer ensemble
Small heat shock proteins (sHsps) form large spherical assemblies and their regulation is not well understood. Here, the authors provide insights into the mechanism of Hsp26 activation by characterising phospho-mimetic mutants of yeast Hsp26. They present cryo-EM structures of the wild-type Hsp26 40mer and its phospho-mimetic mutants that reveal the location of the thermosensor in the oligomer, and the authors also show that the thermosensor domain is targeted by phosphorylation, which relieves the intrinsic inhibition of chaperone activity.
- Moritz Mühlhofer
- , Carsten Peters
- & Johannes Buchner
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Article
| Open AccessHPF1 dynamically controls the PARP1/2 balance between initiating and elongating ADP-ribose modifications
HPF1 controls the ADP-ribosylation activity of PARP1/2 in response to DNA breaks. Here, the authors show that HPF1 regulates the balance between ADP-ribose initiation and elongation through a dynamic interaction that accelerates the initiation rate on serine residues.
- Marie-France Langelier
- , Ramya Billur
- & John M. Pascal
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Article
| Open AccessMDA5 disease variant M854K prevents ATP-dependent structural discrimination of viral and cellular RNA
MDA5 is the primary immune sensor for SARS-CoV-2 and many other viruses. Mutations in MDA5 can cause disease. Here the authors employ CryoEM and biochemical methods to show how steric constraints cause MDA5 to misrecognize endogenous RNA as viral RNA.
- Qin Yu
- , Alba Herrero del Valle
- & Yorgo Modis
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Article
| Open AccessCrystal structures of the elusive Rhizobium etli l-asparaginase reveal a peculiar active site
L-asparaginases catalyse the hydrolysis of L-asparagine to L-aspartic acid and ammonia. Here, the authors present high resolution crystal structures of Rhizobium etli L-asparaginase that contains a Zn2+ binding site without a catalytic role and discuss the catalytic mechanism of the enzyme.
- Joanna I. Loch
- , Barbara Imiolczyk
- & Mariusz Jaskolski
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Article
| Open AccessDistinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization
The V3-crown of the HIV-1 envelope protein largely elicits non-neutralizing antibodies. Here, the authors show that the V3-crown can be targeted by broadly neutralizing designed ankyrin repeat proteins recognizing two conformations one of which resembles CCR5- bound V3.
- Nikolas Friedrich
- , Emanuel Stiegeler
- & Alexandra Trkola
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Article
| Open AccessStructures of prokaryotic ubiquitin-like protein Pup in complex with depupylase Dop reveal the mechanism of catalytic phosphate formation
Pupylation is a bacterial post-translational protein modification, where the small ubiquitin-like protein Pup is covalently attached to lysine side chains of target proteins, which is a reversible process and depupylation is catalysed by the depupylase enzyme, Dop. Here, the authors present crystal structures of Dop in different functional states, which together with biochemical experiments provide insights into the catalytic mechanism of this enzyme.
- Hengjun Cui
- , Andreas U. Müller
- & Eilika Weber-Ban
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Article
| Open AccessAbemaciclib is a potent inhibitor of DYRK1A and HIP kinases involved in transcriptional regulation
Abemaciclib is a third generation CDK-directed drug used in the treatment of HR + /HER2 negative advanced or metastatic breast cancer. Here the authors demonstrate that members of the Homeodomain-interacting protein kinases (HIPKs) HIPK3 and DYRK1A are also targeted by Abemaciclib.
- Ines H. Kaltheuner
- , Kanchan Anand
- & Matthias Geyer
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Article
| Open AccessMechanism of actin-dependent activation of nucleotidyl cyclase toxins from bacterial human pathogens
The nucleotidyl cyclase toxin exoenzyme Y (ExoY), which is secreted by the human pathogens Pseudomonas aeruginosa and Vibrio vulnificus is activated by actin. Here, the authors present the cryo-EM structures of PaExoY bound to F-actin and VvExoY in complex with G-actin-profilin. These structures together with molecular dynamics simulations and enzymatic assays provide insights into the activation mechanism for both bacterial cyclase toxin families that interact with either F- or G-actin.
- Alexander Belyy
- , Felipe Merino
- & Stefan Raunser
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Article
| Open AccessStructural basis of the regulation of the normal and oncogenic methylation of nucleosomal histone H3 Lys36 by NSD2
An upregulation of NSD2, a histone H3 lysine 36 (H3K36) methyltransferase is linked to multiple myeloma and other types of cancer. Here, the authors provide insights into the regulatory mechanism of NSD2 by determining the 2.8 Å cryo-EM structure of the NSD2 bound nucleosome complex, and based on MD simulations they discuss how two oncogenic mutations enhance NSD2 activity.
- Ko Sato
- , Amarjeet Kumar
- & Toru Sengoku
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Article
| Open AccessStructural dynamics in the water and proton channels of photosystem II during the S2 to S3 transition
The oxygen-evolving complex in Photosystem II (PSII) catalyzes the light-driven oxidation of water to oxygen and it is still under debate how the water reaches the active site. Here, the authors analyse time-resolved XFEL-based crystal structures of PSII that were determined at room temperature and report the structures of the waters in the putative channels surrounding the active site at various time-points during the reaction cycle and conclude that the O1 channel is the likely water intake pathway and the Cl1 channel the likely proton release pathway.
- Rana Hussein
- , Mohamed Ibrahim
- & Junko Yano
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Article
| Open AccessStructure of Escherichia coli cytochrome bd-II type oxidase with bound aurachin D
Terminal bd oxidases endow bacterial pathogens with resistance to cellular stressors. The authors report the structure of E. coli bd-II type oxidase with the bound inhibitor aurachin D, providing a structural basis for the design of specifically binding antibiotics.
- Antonia Grauel
- , Jan Kägi
- & Thorsten Friedrich
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Article
| Open AccessCryo-EM structure provides insights into the dimer arrangement of the O-linked β-N-acetylglucosamine transferase OGT
The modification of proteins with O-linked β-N-acetylglucosamine (OGlcNAc) plays roles in regulation of numerous cellular functions while incorrect O-GlcNAcylation patterns are linked to disease. Here, the authors report a cryo-EM structure of full-length O-GlcNAc transferase (OGT), the only enzyme responsible for O-GlcNAcylation.
- Richard W. Meek
- , James N. Blaza
- & Gideon J. Davies
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Article
| Open Access2-Oxoglutarate derivatives can selectively enhance or inhibit the activity of human oxygenases
The human 2-oxoglutarate (2OG) oxygenases FIH and AspH are relevant drug targets. Here, the authors show that synthetic and naturally occurring 2OG derivatives can selectively modulate FIH and AspH activities, suggesting that these compounds may serve as a basis to develop 2OG oxygenase-targeting probes and drugs.
- Yu Nakashima
- , Lennart Brewitz
- & Christopher J. Schofield
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Article
| Open AccessExtended antibody-framework-to-antigen distance observed exclusively with broad HIV-1-neutralizing antibodies recognizing glycan-dense surfaces
Here, the authors analyse the distance between the body of an antibody and a protein antigen denoted as the Antibody-Framework-to-Antigen Distance (AFAD) for about 2000 non-redundant antibody-protein antigen complexes in the Protein Data Bank. They observe that antibodies with exceptionally long AFADs were all broad HIV-1-neutralizing antibodies that targeted densely glycosylated regions on the HIV-1-envelope trimer. The connection between long AFAD and dense glycan was further validated by the cryo-EM structure of antibody 2909 recognizing a glycan hole and by glycan shielding analyses based on molecular dynamics simulations.
- Myungjin Lee
- , Anita Changela
- & Peter D. Kwong
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Article
| Open AccessA site of vulnerability at V3 crown defined by HIV-1 bNAb M4008_N1
Mapping of the HIV Env surface epitopes targeted by broadly neutralizing antibodies (bNAbs) is of great interest for HIV-1 vaccine design. Here, the authors present the 3.2 Å cryo-EM structure of the bNAb M4008_N1 in complex with BG505 DS-SOSIP, an engineered native-like Env trimer and observe that the bNAb epitope is centered at the V3 crown and that M4008_N1 uses its CDR H3 to form an extended β-sheet with the β-hairpin of the V3 crown in a conformation stabilized in the prefusion trimer.
- Kun-Wei Chan
- , Christina C. Luo
- & Xiang-Peng Kong
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Article
| Open AccessNascent chains can form co-translational folding intermediates that promote post-translational folding outcomes in a disease-causing protein
Alpha-1-antitrypsin (AAT) deficiency results from misfolding-prone AAT variants. Here the authors show that AAT forms co-translational folding intermediates on the ribosome that persist upon release and determine its folding fate. They show too that the ribosome can also modulate misfolding-prone AAT intermediates during their synthesis.
- Elena Plessa
- , Lien P. Chu
- & Lisa D. Cabrita
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Article
| Open AccessStructural basis of the interaction between SETD2 methyltransferase and hnRNP L paralogs for governing co-transcriptional splicing
Interaction between SETD2 and hnRNP L has previously been shown to be implicated in coupling gene transcription and mRNA processing. Here the authors elucidate the molecular basis of this functional interaction, showing that the RRM domain of hnRNP L possesses non-overlapping binding interfaces for engaging RNA and SETD2.
- Saikat Bhattacharya
- , Suman Wang
- & Fudong Li
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Article
| Open AccessStructure and activation mechanism of the hexameric plasma membrane H+-ATPase
The plasma membrane H+ -ATPase is responsible for maintenance of the plasma membrane potential, which provides energy for the transport of nutrients, and the plasma membrane H+ -ATPase in S. cerevisiae (Pma1) is a P3A-type ATPase that assembles and functions as a hexamer. Here, the authors present the cryo-EM structures of autoinhibited and activated native Pma1 hexamers purified with endogenous lipids and they propose a mechanism for proton pumping across the membrane by this family of H+ -ATPases.
- Peng Zhao
- , Chaoran Zhao
- & Lin Bai
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Article
| Open AccessRole of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM
Systemic AL amyloidosis is caused by misfolding of immunoglobulin light chains (LCs) but how post-translational modifications (PTMs) of LCs influence amyloid formation is not well understood. Here, the authors present the cryo-EM structure of an AL amyloid fibril derived from the heart tissue of a patient that is partially pyroglutamylated, N-glycosylated and contains an intramolecular disulfide bond. Based on their structure and biochemical experiments the authors conclude that the mutational changes, disulfide bond and glycosylation determine the fibril protein fold and that glycosylation protects the fibril core from proteolytic degradation.
- Lynn Radamaker
- , Sara Karimi-Farsijani
- & Marcus Fändrich
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Article
| Open AccessPseudoknot length modulates the folding, conformational dynamics, and robustness of Xrn1 resistance of flaviviral xrRNAs
Exoribonuclease-resistant RNAs (xrRNAs) are RNA elements that block the exoribonucleolytic degradation of RNA. Here the authors show how a long-range pseudoknot length modulates the Mg2+-dependence of flaviviral xrRNA’s folding, conformational dynamics and Xrn1 resistance.
- Xiaolin Niu
- , Ruirui Sun
- & Xianyang Fang
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Article
| Open AccessStructural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren
Ghrelin is a central orexigenic peptide hormone in human energy homeostasis that is also known as ‘hunger hormone’ and signals through its GPCR, GHSR. Here, the authors present the cryo-EM structures of the human GHSR-Gi signaling complex with bound ghrelin and the synthetic non-peptide agonist ibutamoren that are of interest for drug design.
- Heng Liu
- , Dapeng Sun
- & Cheng Zhang
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Article
| Open AccessShape shifter: redirection of prolate phage capsid assembly by staphylococcal pathogenicity islands
Phage-inducible chromosomal islands (PICIs) are a group of mobile genetic elements that hijack the replication and assembly machinery of helper bacteriophages. Here the authors describe a mechanism by which a group of PICIs from Staphylococcus aureus re-direct the assembly pathway of their helpers using a capsid protein homolog.
- N’Toia C. Hawkins
- , James L. Kizziah
- & Terje Dokland
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Article
| Open AccessMolecular mechanisms of the CdnG-Cap5 antiphage defense system employing 3′,2′-cGAMP as the second messenger
Many bacterial cyclic-oligonucleotide-based antiphage signaling systems (CBASS) employ effectors with SAVED domains. Here, the authors present a biochemical and structural characterization of two such CBASS, providing mechanistic insights into bacterial antiphage defense.
- Shirin Fatma
- , Arpita Chakravarti
- & Raven H. Huang
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Article
| Open AccessA molecular vision of fungal cell wall organization by functional genomics and solid-state NMR
The fungal cell wall is a complex structure composed mainly of glucans, chitin and glycoproteins. Here, the authors use solid-state NMR spectroscopy to assess the cell wall architecture of Aspergillus fumigatus, comparing wild-type cells and mutants lacking major structural polysaccharides, with insights into the distinct functions of these components.
- Arnab Chakraborty
- , Liyanage D. Fernando
- & Tuo Wang
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Article
| Open AccessC-Glycoside metabolism in the gut and in nature: Identification, characterization, structural analyses and distribution of C-C bond-cleaving enzymes
In C-glycosides the sugar moiety is linked through a carbon-carbon bond to the non-sugar moiety, which can be cleaved by intestinal microbes. Here, the authors use bioinformatics analysis to identify C-glycoside deglycosidase enzymes in intestinal and soil bacteria, biochemically characterise them and determine their structures and probe catalytic important residues in mutagenesis experiments.
- Takahiro Mori
- , Takuto Kumano
- & Michihiko Kobayashi
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Article
| Open AccessA previously unrecognized membrane protein in the Rhodobacter sphaeroides LH1-RC photocomplex
Rhodobacter (Rba.) sphaeroides is a model organism for studying bacterial photosynthesis. Here, the authors present the 2.9 Å cryo-EM structure of the monomeric light-harvesting-reaction center core complex from Rba. sphaeroides strain IL106, which revealed the position and conformation of PufX and the presence of an additional component protein-U, an integral membrane protein.
- Kazutoshi Tani
- , Kenji V. P. Nagashima
- & Zheng-Yu Wang-Otomo
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Article
| Open AccessCryoEM structure of the outer membrane secretin channel pIV from the f1 filamentous bacteriophage
New virions of Ff bacteriophages are extruded from the host cell via the channel built from phage protein pIV, homologous to bacterial secretins. Here, the authors report the structure of this channel from the f1 filamentous bacteriophage and propose its use as an adjuvant to increase the uptake and efficacy of antibiotics.
- Rebecca Conners
- , Mathew McLaren
- & Vicki A. M. Gold
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Article
| Open AccessStructural mechanisms of TRPV6 inhibition by ruthenium red and econazole
TRPV6 is a calcium-selective ion channel that is involved in numerous calcium-dependent physiological processes and it is of interest as a potential drug target. Here, the authors present the cryo-EM structures of human TRPV6 with the bound inhibitors ruthenium red and the antifungal drug econazole and discuss their inhibition mechanisms.
- Arthur Neuberger
- , Kirill D. Nadezhdin
- & Alexander I. Sobolevsky
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Article
| Open AccessStructural insights into the clustering and activation of Tie2 receptor mediated by Tie2 agonistic antibody
Angiopoietin (Angpt)-Tie receptor 2 (Tie2) regulates vascular stability and is thus a potential therapeutic target in vascular diseases. Here, the authors report a Tie2-agonistic antibody which targets a site distinct from the Angpt 1-binding site and which influences Tie2 clustering and activation in an Angpt2 inhibition-resistant manner.
- Gyunghee Jo
- , Jeomil Bae
- & Ho Min Kim
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Article
| Open AccessInhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues
The Clostridium difficile virulence factors TcdA and TcdB contain a glucosyltransferase domain (GTD), which has both glucohydrolase (GH) and glucosyltransferase (GT) activities. Here, the authors characterize the transition state features of the TcdA and TcdB GH reactions by measuring kinetic isotope effects and they identify two transition state analogues, isofagomine and noeuromycin that inhibit TcdA and TcdB. They also present the crystal structures of TcdB-GTD bound to these inhibitors and the reaction product UDP.
- Ashleigh S. Paparella
- , Briana L. Aboulache
- & Vern L. Schramm
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Article
| Open AccessDynamic interactions and Ca2+-binding modulate the holdase-type chaperone activity of S100B preventing tau aggregation and seeding
The calcium binding protein S100B is an abundantly expressed protein in the brain and has neuro-protective functions by inhibiting Aβ aggregation and metal ion toxicity. Here, the authors combine cell biology and biochemical experiments with chemical kinetics and NMR measurements and show that S100B protein is an extracellular Tau chaperone and further characterize the interactions between S100B and Tau.
- Guilherme G. Moreira
- , François-Xavier Cantrelle
- & Cláudio M. Gomes
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Article
| Open AccessThe hereditary mutation G51D unlocks a distinct fibril strain transmissible to wild-type α-synuclein
G51D mutation of α-synuclein (α-syn) causes a subset of familial Parkinson’s disease that is characterized by an early onset and rapid progression of the disease. Here, the authors present the cryo-EM structure of full-length G51D α-syn fibrils that is distinct from other known α-syn fibril structures, and they show that G51D fibrils can cross-seed wild-type (WT) α-syn and that these cross-seeded WT fibrils replicate the G51D fibril structure.
- Yunpeng Sun
- , Houfang Long
- & Cong Liu
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Article
| Open AccessStructural basis for high selectivity of a rice silicon channel Lsi1
The rice Lsi1 aquaporin mediates uptake of silicic acid via the roots. Here the authors show the crystal structure of rice Lsi1 and characterize a unique five residue hydrophilic selectivity filter providing a structural basis for the highly selective activity of Lsi1 in Si uptake.
- Yasunori Saitoh
- , Namiki Mitani-Ueno
- & Michihiro Suga
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Article
| Open AccessIon-dependent structure, dynamics, and allosteric coupling in a non-selective cation channel
NaK is a bacterial non-selective cation channel. Here, the authors use solution NMR to show that selectivity filter (SF) in NaK is dynamic, with structural differences between the Na+ and K + -bound states. The conformation of the SF is communicated to the pore-lining helices similarly as in the K + -selective channels.
- Adam Lewis
- , Vilius Kurauskas
- & Katherine Henzler-Wildman
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Article
| Open AccessStructure of PDE3A–SLFN12 complex and structure-based design for a potent apoptosis inducer of tumor cells
Anagrelide, nauclefine and DNMDP induce apoptosis by forming complexes with phosphodiesterase 3A (PDE3A) and Schlafen 12 protein (SLFN12). Here, the authors present the cryo-EM structures of PDE3A-SLFN12 complexes with these compounds as molecular glues. Based on the complex structure, they developed an anagrelide analog that shows a higher potency in inducing apoptosis in cultured cells and also promotes tumor growth inhibition in tumor xenografts, which is of interest for cancer drug development.
- Jie Chen
- , Nan Liu
- & Xiaodong Wang
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Article
| Open AccessStructural basis for protein glutamylation by the Legionella pseudokinase SidJ
Legionella pneumophila (LP) employs the metaeffector SidJ to suppress the toxicity of SdeA and other LP SidE effector family members by catalysing the glutamylation of the catalytic Glu residue. Here, the authors present the cryo-EM structures of SidJ in complex with SdeA in two different states, which together with mutagenesis analysis provide insights into the substrate recognition and the mechanism of protein glutamylation by SidJ.
- Michael Adams
- , Rahul Sharma
- & Sagar Bhogaraju
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Article
| Open AccessThe 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag
The 20S particle is part of the 26S proteasome, but also exists as a free complex. Here, the authors outline signature activities of the 20S and combine chemical, structural, functional and proteomic assays to show that the 20S can degrade ubiquitin tags along with conjugated substrates.
- Indrajit Sahu
- , Sachitanand M. Mali
- & Michael H. Glickman
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Article
| Open AccessStructure of Machupo virus polymerase in complex with matrix protein Z
The RNA polymerase L of arenaviruses is of interest for drug design and its activity is inhibited by the matrix protein Z. Here, the authors present the cryo-EM structure of the Machupo virus polymerase L in complex with matrix protein Z and discuss the inhibitory mechanism.
- Jun Ma
- , Shuangyue Zhang
- & Xinzheng Zhang
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Article
| Open AccessStructural insights into RNA polymerase III-mediated transcription termination through trapping poly-deoxythymidine
Termination of eukaryotic RNA polymerase III (Pol III)-mediated transcription occurs when the polymerase reaches a stretch of four or more deoxythymidine nucleotides (poly-dT) on the non-template strand. Here, the authors present the 3.6 Å cryo-EM structure of a human Pol III pre-termination complex (PTC) that was assembled on a 7 dT-containing DNA template and discuss the mechanism of poly-dT-dependent transcription termination of Pol III.
- Haifeng Hou
- , Yan Li
- & Yanhui Xu
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Article
| Open AccessStructural and functional analysis of target recognition by the lymphocyte adaptor protein LNK
LNK is a potent negative regulator of cytokine signaling implicated in blood cells proliferation. Here the authors present structures of the substrate recognition (SH2) domain of LNK in complex with phosphorylated motifs from JAK2 and EPOR; providing insight into its binding specificity and mode of action.
- Rhiannon Morris
- , Yaoyuan Zhang
- & Jeffrey J. Babon
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Article
| Open AccessMolecular insights into receptor binding of recent emerging SARS-CoV-2 variants
The SARS-CoV-2 spike (S) protein mediates viral entry by binding of its receptor-binding domain (RBD) to the human angiotensin-converting enzyme 2 (ACE2) receptor and mutations of the S protein may have a great impact on virus transmissibility. Here, the authors characterize the interactions of six different SARS-CoV-2 RBD variants among them Alpha, Beta and Gamma and present crystal structures of these ACE2-RBD complexes.
- Pengcheng Han
- , Chao Su
- & Jianxun Qi
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Article
| Open AccessStructural basis of soluble membrane attack complex packaging for clearance
To prevent unregulated complement activation, extracellular chaperones capture soluble precursors to the membrane attack complex (sMAC). Here, structural analysis of sMAC reveals how clusterin recognizes heterogeneous sMAC complexes and inhibits polymerization of complement protein C9.
- Anaïs Menny
- , Marie V. Lukassen
- & Doryen Bubeck
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Article
| Open AccessCryo-EM structure of human Pol κ bound to DNA and mono-ubiquitylated PCNA
Translesion Synthesis is a process that enables cells to overcome the deleterious effects of replication stalling caused by DNA lesions. Here the authors present a Cryo-EM structure of human Y-family DNA polymerase k (Pol k) bound to PCNA, P/T DNA and an incoming nucleotide; and propose a model for polymerase switching in which “carrier state” Pol k is recruited to PCNA.
- Claudia Lancey
- , Muhammad Tehseen
- & Alfredo De Biasio