Featured
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Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir
A biochemical and structural analysis demonstrates that alterations at the substrate-binding pocket of the main protease of SARS-CoV-2 can allow the virus to develop resistance to nirmatrelvir in two distinct ways.
- Yinkai Duan
- , Hao Zhou
- & Haitao Yang
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Article
| Open AccessPhosphoantigens glue butyrophilin 3A1 and 2A1 to activate Vγ9Vδ2 T cells
Phosphoantigen-mediated BTN2A1 association drives BTN3A1 intracellular fluctuations outwards in a thermodynamically favourable manner, thereby enabling BTN3A1 to push off from the BTN2A1 ectodomain to initiate T cell receptor–mediated γδ T cell activation.
- Linjie Yuan
- , Xianqiang Ma
- & Yonghui Zhang
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News & Views |
Dynamic ion channel defies dogma
It is well established that proteins in the TRP family of ion channels assemble from four subunits. But do they always do this? A five-subunit structure has now been observed, and might be involved in channel regulation.
- Ute A. Hellmich
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Article |
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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Research Briefing |
Structure sheds light on a lipid-transport machine in mycobacteria
To cause tuberculosis, the bacterium Mycobacterium tuberculosis must obtain nutrients from host cells. This is facilitated at least in part by protein complexes known as transporters. The structure of one such transporter reveals how its constituent subunits assemble into a large complex that enables lipids to be transported into the bacterium.
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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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News & Views |
Hotly awaited structures obtained for the human protein UCP1
The protein UCP1 helps to release energy as heat in brown fat. Structures of human UCP1 provide crucial information about its mechanism of action, and might aid drug design for obesity and various metabolism-associated complications.
- Michael J. Gaudry
- & Martin Jastroch
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| Open AccessDiverse modes of H3K36me3-guided nucleosomal deacetylation by Rpd3S
Structural and biochemical studies of the Saccharomyces cerevisiae Rpd3 small complex in free and H3K36me3 nucleosome-bound states reveal multiple nucleosome-binding modes and provide insights into mechanisms underlying epigenetic regulation by histone modification.
- Haipeng Guan
- , Pei Wang
- & Haitao Li
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News Feature |
AI tools are designing entirely new proteins that could transform medicine
Digital art techniques can now devise custom, working biomolecules on demand.
- Ewen Callaway
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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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Technology Feature |
Foldseek gives AlphaFold protein database a rapid search tool
The structural search program makes finding proteins with similar 3D shapes easy.
- Matthew Hutson
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Article
| Open AccessFanzor is a eukaryotic programmable RNA-guided endonuclease
Fanzor is shown to be an RNA-guided DNA endonuclease, demonstrating that such endonucleases are found in all domains of life and indicating a potential new tool for genome engineering applications.
- Makoto Saito
- , Peiyu Xu
- & Feng Zhang
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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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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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Structural insights into BCDX2 complex function in homologous recombination
Analyses of the structure and biochemical properties of the tetrameric complex of RAD51B, RAD51C, RAD51D and XRCC2 reveal details of its role in the repair of DNA double-strand breaks.
- Yashpal Rawal
- , Lijia Jia
- & Shaun K. Olsen
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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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| Open AccessStructural basis for FGF hormone signalling
This study reveals how Klotho and heparan sulfate glycosaminoglycan coreceptors enable FGF hormones to induce asymmetric 1:2 FGF–FGFR dimerization mandatory for FGFR kinase activation and hence signalling.
- Lingfeng Chen
- , Lili Fu
- & Moosa Mohammadi
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Cryo-EM structure of SARS-CoV-2 postfusion spike in membrane
The SARS-CoV-2 spike internal fusion peptide forms a hairpin-like wedge that spans almost the entire lipid bilayer and the transmembrane segment wraps around the fusion peptide at the last stage of membrane fusion.
- Wei Shi
- , Yongfei Cai
- & Bing Chen
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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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News & Views |
How a protein differentiates between rare-earth elements
A protein has been discovered that binds to the lighter members of the rare-earth family of metals more strongly than to the heavier ones — an amazing feat, given the chemical similarities of these elements.
- Scott Banta
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Research Briefing |
A structural model of the core of cilia
Axonemes are molecular machines that enable the movement of cilia, the hair-like structures found on the surface of some cells. Atomic models of axonemes from the flagella of green algae and from the cilia of human respiratory-tract cells reveal how the axoneme enables the cilia to move, and explain the effects of genetic mutations that cause human ciliary disease.
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| 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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| Open AccessEnhanced rare-earth separation with a metal-sensitive lanmodulin dimer
A study biochemically and structurally characterizes a lanmodulin from Hansschlegelia quercus with an oligomeric state sensitive to rare-earth ionic radius.
- Joseph A. Mattocks
- , Jonathan J. Jung
- & Joseph A. Cotruvo Jr
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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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Article
| 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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Structural basis of amine odorant perception by a mammal olfactory receptor
Cryo-electron microscopy structures of mouse trace amine-associated receptor 9 reveals structural motifs involved in odorant ligand recognition, including a unique disulfide bond linking the N terminus to extracellular loop 2.
- Lulu Guo
- , Jie Cheng
- & Jin-Peng Sun
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A small-molecule PI3Kα activator for cardioprotection and neuroregeneration
A new specific, small-molecule activator of the PI3Kα isoform (UCL-TRO-1938) identified through high-throughput screening can transiently activate PI3K signalling and biological responses in cells and tissues, with potential therapeutic applications in tissue protection and regeneration.
- Grace Q. Gong
- , Benoit Bilanges
- & Bart Vanhaesebroeck
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Editorial |
For chemists, the AI revolution has yet to happen
Machine-learning systems in chemistry need accurate and accessible training data. Until they get it, they won’t achieve their potential.
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News & Views |
The role of NINJ1 protein in programmed cellular destruction
The protein NINJ1 drives membrane rupture associated with certain types of cell death. Investigation of NINJ1 reveals mechanistic details of how it functions, raising the possibility of developing new therapeutics.
- James C. Whisstock
- & Ruby H. P. Law
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| 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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RNA conformational propensities determine cellular activity
Systematic alteration of HIV-1 TAR RNA and quantitative determination of its propensity to bind to the Tat protein establish a key role role for a rare and short-lived RNA state in Tat-dependent transactivation in cells.
- Megan L. Ken
- , Rohit Roy
- & Hashim M. Al-Hashimi
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EMC chaperone–CaV structure reveals an ion channel assembly intermediate
Interactions between the endoplasmic reticulum membrane protein complex (EMC) and the high-voltage-activated calcium channel CaVα2δ are mutually exclusive, and EMC-to-CaVα2δ hand-off involves a divalent ion-dependent step and CaV1.2 element ordering.
- Zhou Chen
- , Abhisek Mondal
- & Daniel L. Minor Jr
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News & Views |
A clue to the catalytic activation of splicing
The processing of messenger RNA during splicing requires the activity of a complex of RNAs and proteins termed the spliceosome. Structural data shed light on previously mysterious aspects of splicing in humans.
- Soo-Chen Cheng
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In situ architecture of the ER–mitochondria encounter structure
Integrative structural biology combining quantitative live imaging, cryo-correlative microscopy, subtomogram averaging and molecular modelling enables in situ determination of the structure of the endoplasmic reticulum–mitochondria encounter complex in yeast.
- Michael R. Wozny
- , Andrea Di Luca
- & Wanda Kukulski
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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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News |
New cellular ‘organelle’ discovered inside fruit-fly intestines
Fruit-fly cells use previously unknown complex cellular structures to store phosphate, a molecule essential to life
- Gemma Conroy
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News & Views |
Clues to how water splits during photosynthesis
The tools of crystallography, spectroscopy and quantum chemistry are pulling back the curtain on photosynthesis, probing previously elusive catalytic intermediates that arise when water splits to form oxygen.
- Dimitrios A. Pantazis
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Research Briefing |
Structure of the most abundant human gut virus
Crassviruses are the most abundant, and among the most genetically diverse, viruses found in the human gut. New structural information about these viruses has shed light on the functions of previously uncharacterized proteins in virus-particle assembly and infection.
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| 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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| 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