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Featured
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Obituary |
Robert Grubbs (1942–2021)
Nobel prizewinner whose universal catalysts transformed chemistry.
- Parisa Mehrkhodavandi
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Article |
Glioblastoma mutations alter EGFR dimer structure to prevent ligand bias
Extracellular glioblastoma-associated mutations reduce the ability of the epidermal growth factor receptor to distinguish between its ligands.
- Chun Hu
- , Carlos A. Leche II
- & Mark A. Lemmon
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Article
| Open AccessACE2 binding is an ancestral and evolvable trait of sarbecoviruses
ACE2 binding is an ancestral, widespread trait of sarbecovirus receptor-binding domains, and many single mutations enable binding to different ACE2 receptors.
- Tyler N. Starr
- , Samantha K. Zepeda
- & Jesse D. Bloom
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Article |
Structure of a B12-dependent radical SAM enzyme in carbapenem biosynthesis
X-ray crystal structures of TokK, a cobalamin- or B12-dependent radical SAM methylase, provide insight into how these enzymes use sequential radical-mediated methylations to assemble the C6 side chain of carbapenem antibiotics.
- Hayley L. Knox
- , Erica K. Sinner
- & Squire J. Booker
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Article
| Open AccessCrystallographic snapshots of a B12-dependent radical SAM methyltransferase
Structural and spectroscopic studies show how a B12-dependent radical SAM enzyme catalyses unique and challenging alkylation chemistry, including protein post-translational modification required for methane biosynthesis.
- Cameron D. Fyfe
- , Noelia Bernardo-García
- & Olivier Berteau
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Article |
Ageing exacerbates ribosome pausing to disrupt cotranslational proteostasis
Ageing alters the kinetics of translation elongation in both Caenorhabditis elegans and Saccharomyces cerevisiae.
- Kevin C. Stein
- , Fabián Morales-Polanco
- & Judith Frydman
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Article
| Open AccessStructural insights into inhibitor regulation of the DNA repair protein DNA-PKcs
Cryo-electron microscopy structures of DNA-dependent protein kinase catalytic subunit bound to ATPγS and four inhibitors (wortmannin, NU7441, AZD7648 and M3814) provide molecular details and insights useful for drug design.
- Shikang Liang
- , Sherine E. Thomas
- & Tom L. Blundell
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Article |
Time-resolved structural analysis of an RNA-cleaving DNA catalyst
Using high-resolution NMR characterization, the kinetics and dynamics of the catalytic function of a DNAzyme are shown.
- Jan Borggräfe
- , Julian Victor
- & Manuel Etzkorn
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News & Views |
A microbe that uses crude oil to make methane
A microorganism that dwells in an underground oil reservoir has been found to degrade various petroleum compounds and use them to produce methane through a previously unreported biochemical pathway.
- Guillaume Borrel
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Article |
Structure of Hsp90–Hsp70–Hop–GR reveals the Hsp90 client-loading mechanism
The cryo-electron microscopy structure of the glucocorticoid receptor (GR)-loading complex—a complex in which Hsp70 loads GR onto Hsp90 and Hop—is described, providing insights into how the chaperones Hsp90 and Hsp70 coordinate to facilitate GR remodelling for activation.
- Ray Yu-Ruei Wang
- , Chari M. Noddings
- & David A. Agard
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Article |
Structure of Hsp90–p23–GR reveals the Hsp90 client-remodelling mechanism
Studies based on cryo-electron microscopy structures of Hsp90 chaperone complexes reveal the molecular mechanism of the chaperone-mediated maturation of the human glucocorticoid receptor.
- Chari M. Noddings
- , Ray Yu-Ruei Wang
- & David A. Agard
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Obituary |
Donald Caspar (1927–2021)
Crystallographer who defined rules of virus structure.
- Lee Makowski
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Article
| Open AccessHELQ is a dual-function DSB repair enzyme modulated by RPA and RAD51
HELQ is differentially regulated by RAD51, which stimulates helicase activity, and RPA, which inhibits helicase activity and stimulates annealing.
- Roopesh Anand
- , Erika Buechelmaier
- & Simon J. Boulton
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Article |
Activation mechanism of PINK1
Unphosphorylated PINK1 of Pediculus humanus corporis forms a dimerized state before undergoing trans-autophosphorylation, and phosphorylated PINK1 undergoes a conformational change in the N-lobe to produce its phosphorylated, ubiquitin-binding state.
- Zhong Yan Gan
- , Sylvie Callegari
- & David Komander
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Obituary |
Ned Seeman (1945–2021)
Nanotechnologist who built the first self-assembling DNA structures.
- Philip Ball
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News & Views |
Transporter-protein structures show how salt gets a sweet ride into cells
Proteins spanning the membranes of cells of the intestine and kidney use sodium-ion gradients to take up glucose, enabling water absorption, too. The structures of these transporter proteins have now been observed in detail.
- David Drew
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Article |
β-NAD as a building block in natural product biosynthesis
β-Nicotinamide adenine dinucleotide is used as a building block in secondary metabolite biosynthetic pathways for a novel class of natural products.
- Lena Barra
- , Takayoshi Awakawa
- & Ikuro Abe
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Article |
A hormone complex of FABP4 and nucleoside kinases regulates islet function
Hormonal FABP4 is discovered to be a pivotal regulator of an adipose–beta-cell endocrine axis that coordinates energy status and metabolic organ function, and targeting this axis improved metabolic outcomes.
- Kacey J. Prentice
- , Jani Saksi
- & Gökhan S. Hotamisligil
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Article |
Activation of homologous recombination in G1 preserves centromeric integrity
Centromeres are able to recruit the homologous recombination machinery during G1 via CENP-A and HJURP, thereby preserving centromeric integrity even in the absence of a sister chromatid.
- Duygu Yilmaz
- , Audrey Furst
- & Evi Soutoglou
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Article |
De novo protein design by deep network hallucination
The trRosetta neural network was used to iteratively optimise model proteins from random 100-amino-acid sequences, resulting in ‘hallucinated’ proteins, which when expressed in bacteria closely resembled the model structures.
- Ivan Anishchenko
- , Samuel J. Pellock
- & David Baker
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Article |
Mechanism for the activation of the anaplastic lymphoma kinase receptor
Cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography are used to provide structural and mechanistic details of the activation of anaplastic lymphoma kinase by the ligands ALKAL1 and ALKAL2.
- Andrey V. Reshetnyak
- , Paolo Rossi
- & Charalampos G. Kalodimos
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Article |
The human microbiome encodes resistance to the antidiabetic drug acarbose
Bacteria in the human gut and oral microbiome encode enzymes that selectively phosphorylate the antidiabetic drug acarbose—an inhibitor of both human and bacterial α-glucosidases—resulting in its inactivation and limiting the drug's effects on the ability of the host to metabolize complex carbohydrates.
- Jared Balaich
- , Michael Estrella
- & Mohamed S. Donia
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Article |
Structural basis for ligand reception by anaplastic lymphoma kinase
Analysis of crystal structures of anaplastic lymphoma kinase elucidate the mechanism by which ligand binding and the glycine-rich domain regulate its activity.
- Tongqing Li
- , Steven E. Stayrook
- & Daryl E. Klein
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Research Highlight |
Mini-machine can chop and channel proteins
Scientists’ creation can cut proteins into pieces and thread them through a molecular tunnel.
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Research Highlight |
This microbe works a toxic metal into a weapon against its foes
Bacteria that cause hospital infections can process copper into an effective antibiotic.
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Nature Index |
Canada’s scientists are elucidating the dark metabolome
Teams studying the human body at the molecular level are grappling with matter that defies identification.
- James Mitchell Crow
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Article |
Structure, function and pharmacology of human itch receptor complexes
Cryo-electron microscopy structures of the MRGPRX2–Gi1 trimer in complex with polycationic compound 48/80 or inflammatory peptides provide insights into the sensing of cationic allergens by MRGPRX2, potentially facilitating the design of therapies to prevent unwanted pseudoallergic reactions.
- Fan Yang
- , Lulu Guo
- & Jin-Peng Sun
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Article |
Structural insights into Ubr1-mediated N-degron polyubiquitination
Structures of Ubr1 in complex with Ubc2, ubiquitin and two N-degron peptides reveal a Ubc2-binding region and an acceptor ubiquitin-binding loop on Ubr1, providing mechanistic insights into the initiation and elongation steps of ubiquitination catalysed by Ubr1.
- Man Pan
- , Qingyun Zheng
- & Minglei Zhao
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Article |
Target site selection and remodelling by type V CRISPR-transposon systems
Structural studies on Scytonema hofmanni CRISPR-associated transposon protein complexes indicate a mechanism for RNA-guided DNA transposition involving Cas12k, TnsC and TnsB.
- Irma Querques
- , Michael Schmitz
- & Martin Jinek
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Article
| Open AccessB cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity
A paper in Nature demonstrates that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages able to limit anti-tumour T cell cytotoxicity.
- Baihao Zhang
- , Alexis Vogelzang
- & Sidonia Fagarasan
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Article |
Dispatched uses Na+ flux to power release of lipid-modified Hedgehog
Cryo-electron microscopy studies show that dynamic coordination of Na+ in the ion channel of Dispatched homologue 1 and the transmembrane Na+ gradient have key roles in exporting lipid-modified Hedgehog protein signal.
- Qianqian Wang
- , Daniel E. Asarnow
- & Philip A. Beachy
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Article |
SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells
SLC25A39 and its paralogue SLC25A40 have redundant roles in the import of glutathione into mitochondria of mammalian cells.
- Ying Wang
- , Frederick S. Yen
- & Kıvanç Birsoy
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Article
| Open AccessA conserved mechanism for regulating replisome disassembly in eukaryotes
A conserved mechanism for the regulation of replisome disassembly in eukaryotes is shown using cryo-electron microscopy, revealing a role for DNA in the preservation of replisome integrity.
- Michael Jenkyn-Bedford
- , Morgan L. Jones
- & Tom D. Deegan
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Article |
Low glycaemic diets alter lipid metabolism to influence tumour growth
Lien et al. show that low glycemic diets can reduce tumour growth by deregulating lipid metabolism.
- Evan C. Lien
- , Anna M. Westermark
- & Matthew G. Vander Heiden
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Article |
eccDNAs are apoptotic products with high innate immunostimulatory activity
By developing a new eccDNA purification and profiling method, the study revealed close-to-random genomic origination, mechanism of biogenesis and function of eccDNAs.
- Yuangao Wang
- , Meng Wang
- & Yi Zhang
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Research Highlight |
Our enormous fish catches have skewed ocean chemistry
Industrial fishing seems to have altered the processing of biomass in the ocean.
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Article |
Systems-level effects of allosteric perturbations to a model molecular switch
Interface mutations in the GTPase switch protein Gsp1 (the yeast homologue of human RAN) allosterically affect the kinetics of the switch cycle, revealing a systems-level mechanism of multi-specificity.
- Tina Perica
- , Christopher J. P. Mathy
- & Tanja Kortemme
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Article
| Open AccessTransposon-associated TnpB is a programmable RNA-guided DNA endonuclease
The RNA-directed nuclease TnpB from Deinococcus radiodurans can be reprogrammed to cleave DNA target sites in human cells.
- Tautvydas Karvelis
- , Gytis Druteika
- & Virginijus Siksnys
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Spotlight |
China’s data-driven dream to overhaul health care
Collaborations between AI researchers and China’s medical workers are helping to combat diseases such as diabetes and COVID-19.
- Sarah O’Meara
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Article |
A single sulfatase is required to access colonic mucin by a gut bacterium
A single sulfatase produced by a bacterium found in the human colon is essential for degradation of sulfated O-glycans in secreted mucus.
- Ana S. Luis
- , Chunsheng Jin
- & Eric C. Martens
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Article |
Mechanism for Cas4-assisted directional spacer acquisition in CRISPR–Cas
Structures of the Cas4–Cas1–Cas2 complex from Geobacter sulfurreducens show that a 3′-overhang in the protospacer adjacent motif is required for complex assembly and spacer insertion into the CRISPR array.
- Chunyi Hu
- , Cristóbal Almendros
- & Ailong Ke
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Article |
Structures of full-length glycoprotein hormone receptor signalling complexes
Cryo-electron microscopy structures of the luteinizing hormone–choriogonadotropin receptor (LHCGR), in complex with Gs and in various states of activation, reveal a distinct mechanism of receptor activation, with implications for drug discovery.
- Jia Duan
- , Peiyu Xu
- & H. Eric Xu
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Technology Feature |
Single-cell proteomics takes centre stage
Deducing the full protein complement of individual cells has long played second fiddle to transcriptomics. That’s about to change.
- Jeffrey M. Perkel
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Research Highlight |
An unruly painkiller is tamed with inspiration from nature
Scientists borrow features of the body’s receptor for tetrodotoxin to create a useful synthetic structure.
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Article
| Open AccessStructural basis of human transcription–DNA repair coupling
The authors resolve the structure of five complexes containing RNA polymerase II and the CSA and CSB proteins, offering insight into how the repair of DNA lesions is coupled to transcription.
- Goran Kokic
- , Felix R. Wagner
- & Patrick Cramer
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Article
| Open AccessDairying enabled Early Bronze Age Yamnaya steppe expansions
Analysis of ancient proteins suggests that Early Bronze Age dairying and horse domestication catalysed eastern Yamnaya migrations.
- Shevan Wilkin
- , Alicia Ventresca Miller
- & Nicole Boivin
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Article |
Structural basis for tRNA methylthiolation by the radical SAM enzyme MiaB
Crystal structures reveal the catalytic mechanism through which the radical S-adenosylmethionine enzyme MiaB adds a methylthio group onto tRNA.
- Olga A. Esakova
- , Tyler L. Grove
- & Squire J. Booker
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Article |
UTX condensation underlies its tumour-suppressive activity
Phase separation properties are a major determinant of UTX activity in chromatin regulation in tumour suppression, and are dependent on a core intrinsically disordered region of the protein.
- Bi Shi
- , Wei Li
- & Hao Jiang
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