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| Open AccessInactivation of the Kv2.1 channel through electromechanical coupling
The exploration of voltage-gated potassium channels using cryo-electron microscopy and electrophysiology identifies a mechanism of inactivation involved in regulating neuron firing.
- Ana I. Fernández-Mariño
- , Xiao-Feng Tan
- & Kenton J. Swartz
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Article
| Open AccessCryo-EM structures reveal native GABAA receptor assemblies and pharmacology
Using cryo-EM, structures of three major assemblies of type A GABA receptors, which regulate brain excitability, are revealed in the mouse brain and provide a basis for the development of subtype-specific drugs.
- Chang Sun
- , Hongtao Zhu
- & Eric Gouaux
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Structural basis for thioredoxin-mediated suppression of NLRP1 inflammasome
Structural and mutational studies and cellular assays show that the inflammasome sensor NLRP1 forms a complex with thioredoxin, which acts as a negative regulator of inflammasome activity.
- Zhikuan Zhang
- , Takuma Shibata
- & Toshiyuki Shimizu
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Molecular mechanism of de novo replication by the Ebola virus polymerase
A study reports the three-dimensional structure of the Ebola virus polymerase in complex with VP35 and RNA, and reveals features required for initiation of viral replication.
- Qi Peng
- , Bin Yuan
- & Yi Shi
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A pentameric TRPV3 channel with a dilated pore
High-speed atomic force microscopy single-molecule imaging and cryo-EM analysis discover and reveal the structure of a TRPV3 pentamer, providing evidence for a non-canonical pentameric TRP-channel assembly, laying the foundation for new directions in TRP channel research.
- Shifra Lansky
- , John Michael Betancourt
- & Simon Scheuring
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OPA1 helical structures give perspective to mitochondrial dysfunction
Cryo-electron microscopy structures of OPA1, mutations of which are associated with the disease dominant optic atrophy, provide insight into how structural features of OPA1 enable this protein to mediate mitochondrial-membrane fusion and remodelling.
- Sarah B. Nyenhuis
- , Xufeng Wu
- & Jenny E. Hinshaw
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Structural mechanism of mitochondrial membrane remodelling by human OPA1
Human OPA1 embeds itself into cardiolipin-containing membranes through a lipid-binding paddle domain, and OPA1 oligomerization through multiple assembly interfaces promotes the helical assembly of a flexible OPA1 lattice on the membrane, driving mitochondrial fusion in cells.
- Alexander von der Malsburg
- , Gracie M. Sapp
- & Halil Aydin
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Article
| Open AccessTail engagement of arrestin at the glucagon receptor
Structures of the glucagon receptor bound to β-arrestin 1 are reported, providing further information about the arrestin-mediated modulation of G protein-coupled receptors.
- Kun Chen
- , Chenhui Zhang
- & Beili Wu
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GPCR activation and GRK2 assembly by a biased intracellular agonist
Structural studies on the complex containing G-protein-coupled receptor kinase 2 (GRK2), neurotensin receptor 1 (NTSR1), Gαq and the arrestin-biased ligand SBI-553 provide insights into these interactions and a foundation for the design of arrestin-biased ligands for G-protein-coupled receptors.
- Jia Duan
- , Heng Liu
- & H. Eric Xu
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Article
| Open AccessTDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP
Cryo-electron microscopy structures and mass spectrometry analyses show that TAR DNA-binding protein 43 (TDP-43) forms amyloid filaments with a distinct fold in type A frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) compared with TDP-43 filaments in type B FTLD-TDP and amyotrophic lateral sclerosis.
- Diana Arseni
- , Renren Chen
- & Benjamin Ryskeldi-Falcon
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Conserved class B GPCR activation by a biased intracellular agonist
A study reports an orally available small-molecule agonist that binds between a G protein and its receptor, and characterizes this new binding mode.
- Li-Hua Zhao
- , Qian He
- & H. Eric Xu
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Oligomerization-mediated activation of a short prokaryotic Argonaute
Cryo-electron microscopy structures and biochemical analyses provide insight into how short prokaryotic Argonaute proteins are assembled and activated, and reveal that oligomerization has a key role in driving catalytic activity.
- Zhangfei Shen
- , Xiao-Yuan Yang
- & Tian-Min Fu
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Structure of an endogenous mycobacterial MCE lipid transporter
Proteins of the Mycobacterium smegmatis Mce1 system assemble to form an elongated ABC transporter complex that is long enough to span the impermeable mycobacterial cell envelope.
- James Chen
- , Alice Fruhauf
- & Damian C. Ekiert
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Article
| Open AccessCooperation between bHLH transcription factors and histones for DNA access
Cryo-EM structures and analysis provide insight into the mechanisms by which basic helix–loop–helix transcription factors access E-box DNA sequences that are embedded within nucleosomes, and cooperate with other transcription factors.
- Alicia K. Michael
- , Lisa Stoos
- & Nicolas H. Thomä
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Structure and function of the RAD51B–RAD51C–RAD51D–XRCC2 tumour suppressor
Structural and biochemical studies of the RAD51B–RAD51C–RAD51D–XRCC2 complex reveal that it uses coupled RAD51B and RAD51C ATPase activities to promote the nucleation and extension of RAD51 nucleoprotein filaments.
- Luke A. Greenhough
- , Chih-Chao Liang
- & Stephen C. West
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Intricate 3D architecture of a DNA mimic of GFP
X-ray crystallography and cryo-electron microscopy analyses of Lettuce—a DNA mimic of GFP—bound to various fluorophores reveal previously unknown structures of DNA that rival analogous RNAs in complexity.
- Luiz F. M. Passalacqua
- , Michael T. Banco
- & Adrian R. Ferré-D’Amaré
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Structural basis of mitochondrial protein import by the TIM23 complex
The cryo-electron microscopy structure of the mitochondrial TIM23 complex from Saccharomyces cerevisiae shows that Tim17 forms a protein translocation path.
- Sue Im Sim
- , Yuanyuan Chen
- & Eunyong Park
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Structural basis for the binding of DNP and purine nucleotides onto UCP1
Using cryo-electron microscopy, the structures of human UCP1 in the nucleotide-free state, the DNP activator-bound state, and the inhibitory ATP-bound state are resolved, providing details of how purine nucleotides inhibit UCP1.
- Yunlu Kang
- & Lei Chen
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Article
| Open AccessClass B1 GPCR activation by an intracellular agonist
A new intracellular agonist-binding pocket is identified that is common to many G protein-coupled receptors, which will have implications for the development of biased compounds that target this large group of receptors.
- Kazuhiro Kobayashi
- , Kouki Kawakami
- & Osamu Nureki
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Outer membrane utilisomes mediate glycan uptake in gut Bacteroidetes
A structural and functional analysis of the systems involved in oligosaccharide uptake in gut Bacteroidetes describes multicomponent complexes termed utilisomes that include pre-processing and transport subunits.
- Joshua B. R. White
- , Augustinas Silale
- & Neil A. Ranson
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Article
| Open AccessAxonemal structures reveal mechanoregulatory and disease mechanisms
Detailed atomic models of axonemes from algal flagella and human respiratory cilia, which are hair-like protrusions from cells that enable motility and clear mucus from human airways, could provide insights into how they function.
- Travis Walton
- , Miao Gui
- & Alan Brown
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Nuclear export of pre-60S particles through the nuclear pore complex
We report the cryo-electron microscopy structure of native pre-60S particles trapped in the channel of the yeast nuclear pore complex, suggesting a translocation model for the export of pre-60S particles through the complex.
- Zongqiang Li
- , Shuaijiabin Chen
- & Sen-Fang Sui
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| Open AccessHistone modifications regulate pioneer transcription factor cooperativity
Binding of the human pioneer transcription factor OCT4 to nucleosomes containing endogenous DNA sequences causes changes to the nucleosome structure and facilitates the cooperative assembly of multiple pioneer transcription factors, a property that can be affected by histone modifications.
- Kalyan K. Sinha
- , Silvija Bilokapic
- & Mario Halic
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Article
| Open AccessStructural basis of NINJ1-mediated plasma membrane rupture in cell death
Structural, biochemical and mutagenesis studies indicate that, in dying cells, the membrane protein NINJ1 assembles into filaments, disrupting the cell membrane.
- Morris Degen
- , José Carlos Santos
- & Sebastian Hiller
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| Open AccessStructural basis of catalytic activation in human splicing
Cryogenic electron microscopy images of a spliceosome complex undergoing catalytic activation provide mechanistic insight into how the two ATP-dependent RNA helicases involved in this process, PRP2 and Aquarius, work together.
- Jana Schmitzová
- , Constantin Cretu
- & Vladimir Pena
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Article
| Open AccessStructural atlas of a human gut crassvirus
A cryo-electron microscopy reconstruction of the virus ΦcrAss001 provides insights into the functions of the viral gene products in capsid assembly and infection.
- Oliver W. Bayfield
- , Andrey N. Shkoporov
- & Alfred A. Antson
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Article
| Open AccessLigand and G-protein selectivity in the κ-opioid receptor
Active-state structures of the κ-opioid receptor in complexes with the G-protein heterotrimers Gi1, GoA, Gz and Gg provide insights into the actions of hallucinogenic opioids and G-protein-coupling specificity at the κ-opioid receptor.
- Jianming Han
- , Jingying Zhang
- & Tao Che
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Cryptochrome–Timeless structure reveals circadian clock timing mechanisms
Structural analysis of a protein complex in the circadian clock of Drosophila reveals how a light-sensing cryptochrome recognizes and engages its target.
- Changfan Lin
- , Shi Feng
- & Brian R. Crane
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Structural basis of BAM-mediated outer membrane β-barrel protein assembly
The structural basis of the late-stage intermediate assembly of outer membrane β-barrel proteins mediated by the bacterial β-barrel assembly machinery is determined.
- Chongrong Shen
- , Shenghai Chang
- & Haohao Dong
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Structural basis of sensory receptor evolution in octopus
Cryo-electron microscopy analyses reveal adaptations that facilitate the octopus chemotactile receptor’s evolutionary transition from an ancestral role in neurotransmission to detecting greasy environmental agonists for ‘taste by touch’ sensory behaviour.
- Corey A. H. Allard
- , Guipeun Kang
- & Nicholas W. Bellono
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Sensory specializations drive octopus and squid behaviour
Octopus and squid use cephalopod-specific chemotactile receptors to sense their respective marine environments, but structural adaptations in these receptors support the sensation of specific molecules suited to distinct physiological roles.
- Guipeun Kang
- , Corey A. H. Allard
- & Ryan E. Hibbs
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mRNA recognition and packaging by the human transcription–export complex
Cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNA ribonucleoprotein complexes bound to the transcription–export complex reveal how mRNAs are packaged and recognized for nuclear export.
- Belén Pacheco-Fiallos
- , Matthias K. Vorländer
- & Clemens Plaschka
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Article
| Open AccessCryo-EM structure of the transposon-associated TnpB enzyme
Cryo-electron microscopy analysis of the Deinococcus radiodurans ISDra2 TnpB in complex with its cognate ωRNA and target DNA provides insights into the mechanism of TnpB function and the evolution of CRISPR–Cas12 effectors.
- Ryoya Nakagawa
- , Hisato Hirano
- & Osamu Nureki
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Article
| Open AccessmRNA decoding in human is kinetically and structurally distinct from bacteria
The reaction coordinate of aminoacyl-tRNA movement is altered on the human ribosome and the process is an order of magnitude slower compared with bacteria due to eukaryote-specific structural elements in the human ribosome and in the elongation factor eEF1A.
- Mikael Holm
- , S. Kundhavai Natchiar
- & Scott C. Blanchard
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Article
| Open AccessStructural basis for GSDMB pore formation and its targeting by IpaH7.8
The authors report the cryogenic electron microscopy structures of human GSDMB in complex with Shigella IpaH7.8 and the GSDMB pore, shedding light on the molecular mechanisms of Shigella IpaH7.8 recognition and targeting of GSDMs and GSDMB pore formation.
- Chengliang Wang
- , Sonia Shivcharan
- & Jianbin Ruan
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Article
| Open AccessStructural basis of mitochondrial membrane bending by the I–II–III2–IV2 supercomplex
A supercomplex comprising all four respiratory chain components contributes to the induction of mitochondrial membrane curvature and tubulation of cristae.
- Alexander Mühleip
- , Rasmus Kock Flygaard
- & Alexey Amunts
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Structural and mechanistic insights into fungal β-1,3-glucan synthase FKS1
Using cryo-electron microscopy, the molecular architecture and catalytic mechanism of action of the fungal β-1,3-glucan synthase FKS1 are determined.
- Xinlin Hu
- , Ping Yang
- & Hongjun Yu
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Immunoglobulin M perception by FcμR
The structural basis for the molecular mechanism of recognition of different IgM forms by the IgM receptor FcμR is determined using crystallography and cryo-electron microscopy.
- Yaxin Li
- , Hao Shen
- & Junyu Xiao
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Article
| Open AccessCFTR function, pathology and pharmacology at single-molecule resolution
A structure–function analysis of cystic fibrosis transmembrane conductance regulator shows its two nucleotide-binding domains dimerize before channel opening, and reveals a mechanism through which conformational changes in the channel regulate chloride conductance.
- Jesper Levring
- , Daniel S. Terry
- & Jue Chen
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Structural basis of odorant recognition by a human odorant receptor
Through the use of cryo-electron microscopy and molecular dynamics stimulations, mechanistic insight into the binding of an odorant to the human odorant receptor OR51E2 is provided.
- Christian B. Billesbølle
- , Claire A. de March
- & Aashish Manglik
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In situ structure of the red algal phycobilisome–PSII–PSI–LHC megacomplex
In situ structures of PBS–PSII–PSI–LHC megacomplexes from the alga P. purpureum at near-atomic resolution using cryogenic-electron tomography and in situ single-particle analysis are reported, providing interaction details between PBS, PSII and PSI.
- Xin You
- , Xing Zhang
- & Sen-Fang Sui
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Article
| Open AccessStructural basis for bacterial energy extraction from atmospheric hydrogen
Structural and biochemical studies of the Mycobacterium smegmatis hydrogenase Huc provides insights into how [NiFe] hydrogenases oxidize trace amounts of atmospheric hydrogen and transfer the electrons liberated via quinone transport.
- Rhys Grinter
- , Ashleigh Kropp
- & Chris Greening
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Structure of the human DICER–pre-miRNA complex in a dicing state
The active-state structure of human DICER bound to pre-miRNA reveals the structural basis for the specificity of DICER in how it selects substrates in a sequence dependent manner, and sheds light on DICER-related diseases.
- Young-Yoon Lee
- , Hansol Lee
- & Soung-Hun Roh
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Structure and thiazide inhibition mechanism of the human Na–Cl cotransporter
Using cryo-electron microscopy, the structures of human Na–Cl cotransporter are determined alone and in complex with a thiazide diuretic.
- Minrui Fan
- , Jianxiu Zhang
- & Liang Feng
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An E1–E2 fusion protein primes antiviral immune signalling in bacteria
This study demonstrates that bacteria use a ubiquitin transferase-like enzyme to prime cGAS/DncV-like nucleotidyltransferase activation and use a deubiquitinase-like enzyme to decrease activity.
- Hannah E. Ledvina
- , Qiaozhen Ye
- & Aaron T. Whiteley
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Article
| Open AccessThe structural basis for HIV-1 Vif antagonism of human APOBEC3G
The authors report the cryo-EM structure of human A3G bound to HIV-1 Vif, and the hijacked cellular proteins that promote ubiquitin-mediated proteolysis, suggesting how Vif antagonizes A3G by intercepting it to prevent viral restriction.
- Yen-Li Li
- , Caroline A. Langley
- & John D. Gross
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Structural basis for substrate selection by the SARS-CoV-2 replicase
Cryo-EM is used to visualize the SARS-CoV-2 RTC bound to each of the natural NTPs as well as remdesivir triphosphate (RDV-TP) in states poised for incorporation, explaining the interactions required for NTP recognition and RDV-TP selectivity.
- Brandon F. Malone
- , Jason K. Perry
- & Seth A. Darst
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Architecture of chloroplast TOC–TIC translocon supercomplex
A cryo-electron microscopy analysis of the Chlamydomonas reinhardtii TOC–TIC supercomplex reveals that Tic214 traverses the chloroplast inner membrane, the intermembrane space and the outer membrane, connecting the TOC complex with the TIC proteins.
- Hao Liu
- , Anjie Li
- & Zhenfeng Liu
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Article
| Open AccessStructure of the lysosomal mTORC1–TFEB–Rag–Ragulator megacomplex
Cryogenic-electron microscopy is used to determine the structure of TFEB as presented to mTORC1 for phosphorylation and an explanation is found for the strong dependence of TFEB phosphorylation on FLCN and the RagC GDP state.
- Zhicheng Cui
- , Gennaro Napolitano
- & James H. Hurley