Featured
-
-
Letter |
Low-barrier hydrogen bonds in enzyme cooperativity
Structural and biophysical studies reveal that low-barrier hydrogen bonds enable long-range communication between the active sites of multimeric enzymes and synchronise catalysis.
- Shaobo Dai
- , Lisa-Marie Funk
- & Kai Tittmann
-
Letter |
Structure and mechanism of mitochondrial proton-translocating transhydrogenase
The structure of a mammalian proton-translocating transhydrogenase in various conformations is solved by cryo-electron microscopy, and a mechanism for the coupling process within the enzyme is proposed.
- Domen Kampjut
- & Leonid A. Sazanov
-
Letter |
Inhibition of bacterial ubiquitin ligases by SidJ–calmodulin catalysed glutamylation
In cells infected with Legionella pneumophila, the pseudo kinase SidJ is activated upon forming a complex with human calmodulin and catalyses glutamylation of SidE ubiquitin ligases, which abolishes the activity of these enzymes.
- Sagar Bhogaraju
- , Florian Bonn
- & Ivan Dikic
-
Article |
Structure and autoregulation of a P4-ATPase lipid flippase
Cryo-EM structures of the yeast P4-ATPase Drs2p–Cdc50p in three different states of activation provide insights into the function of this lipid flippase, including mechanisms of autoinhibition and PI4P-dependent activation.
- Milena Timcenko
- , Joseph A. Lyons
- & Poul Nissen
-
Letter |
Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle
Crystal structures of ATP citrate lyase from bacteria, archaea and humans unravel how the enzyme directs the formation of the central metabolite acetyl-CoA, and shed light onto the evolutionary origins of the Krebs cycle.
- Koen H. G. Verschueren
- , Clement Blanchet
- & Kenneth Verstraete
-
Letter |
A kiwellin disarms the metabolic activity of a secreted fungal virulence factor
A kiwellin protein in maize is found to inhibit the activity of the secreted enzyme chorismate mutase from a maize-infecting pathogenic fungus, suggesting a role for kiwellins in plant immunity.
- Xiaowei Han
- , Florian Altegoer
- & Gert Bange
-
Letter |
Structures of an RNA polymerase promoter melting intermediate elucidate DNA unwinding
Cryo-electron microscopy structures of bacterial RNAP–promoter DNA complexes, including structures of partially melted intermediates, suggest a universally conserved common mechanism for promoter DNA opening prior to gene expression.
- Hande Boyaci
- , James Chen
- & Elizabeth A. Campbell
-
Article |
Structural plasticity of D3–D14 ubiquitin ligase in strigolactone signalling
The plant F-box protein D3 has a C-terminal α-helix that switches between two conformational states, allowing the α/β hydrolase D14 to recruit the transcription repressor D53 for strigolactone-dependent degradation.
- Nitzan Shabek
- , Fabrizio Ticchiarelli
- & Ning Zheng
-
Letter |
The entropic force generated by intrinsically disordered segments tunes protein function
The carboxy terminus of human UDP-α-d-glucose-6-dehydrogenase is structurally disordered, but has sequence-independent effects on the conformation of the enzyme and binding of an allosteric inhibitor, suggesting a reason for the persistence of intrinsically disordered peptide segments in the proteome.
- Nicholas D. Keul
- , Krishnadev Oruganty
- & Zachary A. Wood
-
Letter |
Metal-free ribonucleotide reduction powered by a DOPA radical in Mycoplasma pathogens
A subclass of ribonucleotide reductase in Mycoplasma pathogens contains a stable radical formed from a modified tyrosine residue, overturning the presumed requirement for a dinuclear metal site in aerobic ribonucleotide reductase.
- Vivek Srinivas
- , Hugo Lebrette
- & Martin Högbom
-
Article |
Transcription factor dimerization activates the p300 acetyltransferase
The activation of the histone acetyltransferase p300 depends on the activation and oligomerization status of transcription factor ligands.
- Esther Ortega
- , Srinivasan Rengachari
- & Daniel Panne
-
Letter |
Handover mechanism of the growing pilus by the bacterial outer-membrane usher FimD
The structure of a pilus assembly intermediate reveals the timing of subunit polymerization and how chaperone–subunit complexes are transferred from N-terminal to C-terminal domains of the usher in the formation of bacterial pili.
- Minge Du
- , Zuanning Yuan
- & Huilin Li
-
Article |
Tc toxin activation requires unfolding and refolding of a β-propeller
A high-resolution cryo-electron microscopy structure of a complete Tc holotoxin complex reveals the precise mechanism of Tc toxin assembly, gate opening and release of the cytotoxic enzyme into the translocation channel.
- Christos Gatsogiannis
- , Felipe Merino
- & Stefan Raunser
-
Letter |
Ring nucleases deactivate type III CRISPR ribonucleases by degrading cyclic oligoadenylate
In the CRISPR type III system, ‘ring’ nucleases possess a metal-independent mechanism that cleaves cyclic oligoadenylate ring molecules to switch off the antiviral state in cells.
- Januka S. Athukoralage
- , Christophe Rouillon
- & Malcolm F. White
-
Letter |
Automethylation-induced conformational switch in Clr4 (Suv39h) maintains epigenetic stability
An autoinhibitory conformation of the histone H3K9 methyltransferase Clr4 of Schizosaccharomyces pombe helps to prevent aberrant heterochromatin formation and maintains epigenetic stability.
- Nahid Iglesias
- , Mark A. Currie
- & Danesh Moazed
-
Letter |
A naturally occurring antiviral ribonucleotide encoded by the human genome
Viperin inhibits the replication of various viruses by catalysing the conversion of CTP to ddhCTP, which is a unique nucleotide that functions as replication-chain terminator of RNA-dependent RNA polymerases.
- Anthony S. Gizzi
- , Tyler L. Grove
- & Steven C. Almo
-
Letter |
Insights into catalysis and function of phosphoribosyl-linked serine ubiquitination
Structural and functional investigations demonstrate how bacterial enzymes ubiquitinate host proteins.
- Sissy Kalayil
- , Sagar Bhogaraju
- & Ivan Dikic
-
Letter |
Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity
Non-lysine ubiquitination activity of the E3 ubiquitin ligase MYCBP2 is identified by activity-based profiling; biochemical and structural analysis of MYCBP2 suggests the basis for its mechanism and specificity.
- Kuan-Chuan Pao
- , Nicola T. Wood
- & Satpal Virdee
-
Article |
Architecture of the human GATOR1 and GATOR1–Rag GTPases complexes
Cryo-electron microscopy and biochemical analyses of the GATOR1 protein complex reveal that two binding modes underpin its ability to regulate Rag GTPases as a GTPase-activating protein for RAGA.
- Kuang Shen
- , Rick K. Huang
- & David M. Sabatini
-
Letter |
The mechanism of eukaryotic CMG helicase activation
In vitro experiments, using purified proteins and an assay that detects DNA unwinding, reveal the mechanism of activation of eukaryotic DNA replication.
- Max E. Douglas
- , Ferdos Abid Ali
- & John F. X. Diffley
-
Letter |
MEK drives BRAF activation through allosteric control of KSR proteins
KSR–MEK complexes allosterically activate BRAF through the action of N-terminal regulatory region and kinase domain contacts, thus challenging the accepted role of KSR as a scaffold for MEK recruitment to RAF.
- Hugo Lavoie
- , Malha Sahmi
- & Marc Therrien
-
Article |
Dynamic basis for dG•dT misincorporation via tautomerization and ionization
A kinetic model is proposed to predict the probability of dG•dT misincorporation across different polymerases, and provides mechanisms for sequence-dependent misincorporation.
- Isaac J. Kimsey
- , Eric S. Szymanski
- & Hashim M. Al-Hashimi
-
Letter |
Atomic structure of the eukaryotic intramembrane RAS methyltransferase ICMT
The X-ray structure of the integral membrane protein isoprenylcysteine carboxyl methyltransferase suggests mechanisms by which it recognizes both water-soluble and membrane-bound reactants to catalyze the methylation of RAS and other CAAX proteins at the membrane-cytosol interface.
- Melinda M. Diver
- , Leanne Pedi
- & Stephen B. Long
-
Article |
Dynamics of P-type ATPase transport revealed by single-molecule FRET
Single-molecule fluorescence resonance energy transfer is used to identify the rate-limiting step and new intermediates in the conformational cycle of the Listeria monocytogenes calcium transporter LMCA1.
- Mateusz Dyla
- , Daniel S. Terry
- & Scott C. Blanchard
-
Letter |
Enhanced proofreading governs CRISPR–Cas9 targeting accuracy
A new engineered version of SpCas9, called HypaCas9, displays enhanced accuracy of editing without significant loss of efficiency at the desired target.
- Janice S. Chen
- , Yavuz S. Dagdas
- & Jennifer A. Doudna
-
Letter |
SAM-dependent enzyme-catalysed pericyclic reactions in natural product biosynthesis
The enzyme LepI is found to be capable of catalysing several natural-product pericyclic transformations, including a hetero-Diels–Alder reaction and a retro-Claisen rearrangement.
- Masao Ohashi
- , Fang Liu
- & Yi Tang
-
Letter |
How type II CRISPR–Cas establish immunity through Cas1–Cas2-mediated spacer integration
Several structures of the Enteroccocus faecalis Cas1–Cas2 proteins are solved, and help to define the spacer integration mechanisms of type II CRISPR systems.
- Yibei Xiao
- , Sherwin Ng
- & Ailong Ke
-
Article |
A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis
The biosynthesis of oxetanocin A involves OxsB, a B12-dependent S-adenosylmethionine radical enzyme, which catalyses an unusual ring contraction of a 2′-deoxyadenosine phosphate.
- Jennifer Bridwell-Rabb
- , Aoshu Zhong
- & Hung-wen Liu
-
Article |
In-crystal reaction cycle of a toluene-bound diiron hydroxylase
Crystal structures and DFT calculations suggest a possible mechanism for diiron enzyme arene hydroxylation.
- Justin F. Acheson
- , Lucas J. Bailey
- & Brian G. Fox
-
Letter |
Structural insights into adiponectin receptors suggest ceramidase activity
Structures of the adiponectin receptors ADIPOR1 and ADIPOR2 combined with molecular dynamics simulations and enzymatic assays suggest that both receptors have intrinsic ceramidase activity.
- Ieva Vasiliauskaité-Brooks
- , Remy Sounier
- & Sébastien Granier
-
Letter |
Basis of catalytic assembly of the mitotic checkpoint complex
The near-complete in vitro reconstitution of the mitotic spindle assembly checkpoint reveals how the assembly of its effector, the mitotic checkpoint complex, is catalysed.
- Alex C. Faesen
- , Maria Thanasoula
- & Andrea Musacchio
-
Letter |
Structural basis of co-translational quality control by ArfA and RF2 bound to ribosome
The structure of the bacterial ribosome in complex with the ArfA and the release factor RF2 shows how ArfA recruits RF2 to terminate translation of messenger RNAs that lack a stop codon in the ribosome.
- Fuxing Zeng
- , Yanbo Chen
- & Hong Jin
-
Letter |
An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzyme
Characterization of the first Per-ARNT-Sim enzyme, a haem-dependent oxidative N-demethylase.
- Mary Ortmayer
- , Pierre Lafite
- & David Leys
-
Letter |
Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne
The structures of the deubiquitinating enzyme Cezanne alone or in complex with its substrate or product are solved, showing how Cezanne specifically targets Lys11-linked polyubiquitin.
- Tycho E. T. Mevissen
- , Yogesh Kulathu
- & David Komander
-
Article |
The architecture of the mammalian respirasome
Respirasomes are supercomplexes of mitochondrial electron transport chain complexes that are responsible for cellular respiration and energy production; a cryo-electron microscopy structural study of the respirasome is presented.
- Jinke Gu
- , Meng Wu
- & Maojun Yang
-
Article |
Capturing a substrate in an activated RING E3/E2–SUMO complex
A new method based on protein engineering to trap an intact complex between Siz1, SUMO-bound E2, and PCNA for structure determination.
- Frederick C. Streich Jr
- & Christopher D. Lima
-
Letter |
Reconstruction of bacterial transcription-coupled repair at single-molecule resolution
Single-molecule assays show that the recruitment of UvrA and UvrAB to Mfd–RNA polymerase complex formed on a DNA lesion arrests the translocating complex and causes its dissolution.
- Jun Fan
- , Mathieu Leroux-Coyau
- & Terence R. Strick
-
Letter |
The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA
The CRISPR-associated protein Cpf1 from Francisella novicida is a novel enzyme with specific, dual-endoribonuclease–endonuclease activities in precursor crRNA processing and crRNA-programmable cleavage of target DNA.
- Ines Fonfara
- , Hagen Richter
- & Emmanuelle Charpentier
-
Article |
Cullin–RING ubiquitin E3 ligase regulation by the COP9 signalosome
Much of the intracellular protein degradation in eukaryotes is controlled by cullin–RING ubiquitin ligases (CRLs), a vast class of enzymes which are regulated by the COP9 signalosome (CSN); structural characterization of CSN–N8CRL4A complexes by cryo-electron microscopy reveals an induced-fit mechanism of CSN activation triggered only by catalytically activated CRLs without bound substrate, explaining how CSN acts as a global regulator of CRLs.
- Simone Cavadini
- , Eric S. Fischer
- & Nicolas H. Thomä
-
Article |
Structural basis for activity regulation of MLL family methyltransferases
Crystal structures of the SET domains of MLL3 and a mutant MLL1 either unbound or complexed with domains from RBBP5 and ASH2L are determined; a combination of structural, biochemical and computational analyses reveals a two-step activation mechanism of MLL family proteins, which may be relevant for other histone methyltransferases.
- Yanjing Li
- , Jianming Han
- & Ming Lei
-
Letter |
Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function
An unexpected octameric integrase architecture for the betaretrovirus mouse mammary tumour virus intasome.
- Allison Ballandras-Colas
- , Monica Brown
- & Alan N. Engelman
-
Letter |
Structure of a HOIP/E2~ubiquitin complex reveals RBR E3 ligase mechanism and regulation
The first structure of fully active HOIP of the RBR family of RING-type E3 ligases in its transfer complex with an E2~ubiquitin conjugate provides insights into its mechanism of action, including the ideal alignment of the E2 and E3 catalytic centres for ubiquitin transfer and the allosteric regulation of the RBR family.
- Bernhard C. Lechtenberg
- , Akhil Rajput
- & Stefan J. Riedl
-
Article |
Basomedial amygdala mediates top-down control of anxiety and fear
Activation of the ventral medial prefrontal cortex–basomedial amygdala pathway is shown to suppress anxiety and fear-related freezing in mice, thus identifying the basomedial amygdala (and not intercalated cells, as posited by earlier models) as a novel target of top-down control.
- Avishek Adhikari
- , Talia N. Lerner
- & Karl Deisseroth
-
Letter |
RETRACTED ARTICLE: Endoperoxide formation by an α-ketoglutarate-dependent mononuclear non-haem iron enzyme
The X-ray crystal structures of FtmOx1, the first known α-ketoglutarate-dependent mononuclear non-haem iron enzyme that can catalyse an endoperoxide formation reaction, are presented, along with further biochemical analyses which reveal the catalytic versatility of mononuclear non-haem iron enzymes, and help to unravel the mechanisms of endoperoxide biosyntheses.
- Wupeng Yan
- , Heng Song
- & Yan Jessie Zhang
-
Letter |
Structural insight into substrate preference for TET-mediated oxidation
In DNA demethylation, human TET proteins are evolutionarily tuned to be less reactive towards 5hmC and facilitate its generation as a potentially stable mark for regulatory functions.
- Lulu Hu
- , Junyan Lu
- & Yanhui Xu
-
Letter |
The DNA glycosylase AlkD uses a non-base-flipping mechanism to excise bulky lesions
Crystal structures of the DNA glycosylase AlkD with DNA containing various modified bases show that neither substrate recognition nor catalysis use a base-flipping mechanism; instead, AlkD scans the phosphodeoxyribose backbone for increased cationic charge imparted by the alkylated base, and then uses the positive charge to facilitate cleavage of the glycosidic bond, thus explaining the specificity of AlkD for cationic lesions.
- Elwood A. Mullins
- , Rongxin Shi
- & Brandt F. Eichman
-
Letter |
Foreign DNA capture during CRISPR–Cas adaptive immunity
The structure of the Cas1–Cas2 complex bound to a protospacer sequence illustrates how foreign DNA is captured and measured by bacterial proteins in preparation for integration into CRISPR loci.
- James K. Nuñez
- , Lucas B. Harrington
- & Jennifer A. Doudna
-
Letter |
Replisome speed determines the efficiency of the Tus−Ter replication termination barrier
The Tus–Ter termination site of Escherichia coli is not completely efficient in stopping DNA replication, with about half of replisomes bypassing this blockade; here the speed of the replication machinery is shown to determine the outcome of the encounter between the replisome and Tus–Ter.
- Mohamed M. Elshenawy
- , Slobodan Jergic
- & Samir M. Hamdan
-
Article |
Structural insights into the bacterial carbon–phosphorus lyase machinery
The crystal structure of the 240-kilodalton C–P lyase core complex from the bacterium E. coli offers insights into the relatively unknown mechanisms of the enzymatic machinery that allows some microbes to extract phosphate from phosphonate compounds.
- Paulina Seweryn
- , Lan Bich Van
- & Ditlev E. Brodersen
eIF5B gates the transition from translation initiation to elongation