Structural biology articles within Nature Communications

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  • Article
    | Open Access

    Type 2 DNA topoisomerases (Top2) regulates DNA topology during DNA replication, transcription, and chromosome segregation. Here the authors describe a complete structure of the catalytic core of the human Topo IIα bound to DNA and etoposide, providing insight into the regulation of Topo IIα activities and how opening of the DNA-gate is spatially connected to the ATPase domain.

    • Arnaud Vanden Broeck
    • , Christophe Lotz
    •  & Valérie Lamour

  • Article
    | Open Access

    Human leukotriene B4 receptors (BLT1 and BLT2) are members of the GPCR superfamily that respond to a potent pro-inflammatory lipid and chemoattractant LTB4. Here authors determined a crystal structure of the human BLT1 in complex with a selective antagonist MK-D-046 and provide insights into hBLT1 ligand recognition and its mechanism of action.

    • Nairie Michaelian
    • , Anastasiia Sadybekov
    •  & Vadim Cherezov

  • Article
    | Open Access

    Regulation of the MLL family of histone H3K4 methyltransferases on the nucleosome core particle (NCP) remains largely unknown. Here the authors show that intrinsically disordered regions of ASH2L and DPY30 restrict the rotational dynamics of MLL1 on the NCP, allowing more efficient enzyme-substrate engagement and higher H3K4 trimethylation activity.

    • Young-Tae Lee
    • , Alex Ayoub
    •  & Yali Dou

  • Article
    | Open Access

    In placental malaria, interactions between parasite protein VAR2CSA and human glycosaminoglycan chondroitin sulfate A (CS) sequesters infected red blood cells in the placenta. Here, the authors provide cryo-EM structures of VAR2CSA and placental CS, identifying molecular interactions that could guide design of placental malaria vaccines.

    • Kaituo Wang
    • , Robert Dagil
    •  & Ali Salanti

  • Article
    | Open Access

    Small-angle X-ray scattering (SAXS) combines the high tissue penetration of X-rays with specificity to periodic nanostructures. The authors use SAXS tensor tomography (SAXS-TT) on intact mouse and human brain tissue samples, to quantify myelin levels and determine myelin integrity, myelinated axon orientation, and fibre tracts non-destructively.

    • Marios Georgiadis
    • , Aileen Schroeter
    •  & Markus Rudin

  • Article
    | Open Access

    The Multiple Peptide Resistance Factors (MprFs) utilize two separate domains to synthesize and translocate aminoacyl phospholipids to the outer leaflets of bacterial membranes. Here authors present cryo-electron microscopy structures of MprF homodimer from Rhizobium tropici (RtMprF) at two different states in complex with lysyl-phosphatidylglycerol (LysPG).

    • Danfeng Song
    • , Haizhan Jiao
    •  & Zhenfeng Liu

  • Article
    | Open Access

    Although enterovirus D68 poses a major global threat to children, neither vaccines nor therapeutics are currently available. Using Cryo-EM, Zhang et al. show that two murine-derived monoclonal antibodies with therapeutic efficacy neutralize virions via binding to the canyon region, creating steric hindrance for sialic acid receptor binding.

    • Chao Zhang
    • , Cong Xu
    •  & Zhong Huang

  • Article
    | Open Access

    During clathrin-mediated endocytosis in yeast, endocytic coat adaptors, Sla2 and Ent1, must remain attached to the plasma membrane to transmit force from the actin cytoskeleton required for membrane invagination. Here authors present a cryo-EM structure of a 16-mer complex of the ANTH and ENTH membrane-binding domains from Sla2 and Ent1 bound to PIP2 that constitutes the anchor to the plasma membrane.

    • Javier Lizarrondo
    • , David P. Klebl
    •  & Maria M. Garcia-Alai

  • Article
    | Open Access

    Resolving nucleosomes with chemical accuracy inside sub-Mb chromatin provides molecular insight into the modulation of chromatin structure and its liquid–liquid phase separation (LLPS). By developing a multiscale chromatin model, the authors find that DNA breathing enhances the valency, heterogeneity, and dynamics of nucleosomes, promoting disordered folding and LLPS.

    • Stephen E. Farr
    • , Esmae J. Woods
    •  & Rosana Collepardo-Guevara

  • Article
    | Open Access

    The Vip3 family proteins from Bacillus thuringiensis are thought to exert their insecticidal activity through pore formation. Here authors present cryo-EM structures of a Vip3 family toxin in both inactive and activated forms and show the activated Vip3Bc1 in its pore forming conformation on the membrane.

    • Matthew J. Byrne
    • , Matthew G. Iadanza
    •  & Rebecca F. Thompson

  • Article
    | Open Access

    SARS-CoV-2 orf9b binds to the mitochondrial outer membrane protein TOM70 and has been linked to the suppression of interferon responses. Here, the authors characterize the interactions of SARS-CoV-2 orf9b and human TOM70 biochemically, and they determine the 2.2 Å crystal structure of the TOM70 cytosolic domain with a bound SARS-CoV-2 orf9b peptide.

    • Xiaopan Gao
    • , Kaixiang Zhu
    •  & Sheng Cui

  • Article
    | Open Access

    TMEM16 lipid scramblases transport lipids and also operate as ion channels with highly variable ion selectivities and various physiological functions. Using computational electrophysiology simulations, the authors identify the main ion-conductive state of TMEM16 lipid scramblases and find that lipid headgroups modulate ion permeability and regulate ion selectivity of TMEM16 proteolipidic pores.

    • Andrei Y. Kostritskii
    •  & Jan-Philipp Machtens

  • Article
    | Open Access

    Pinoresinol–lariciresinol reductases (PLRs) are enzymes involved in the lignan biosynthesis. Here, crystal structures of three PLRs in the apo, substrate-bound and product-bound states, and accompanying mutagenesis provide insight into PLRs catalytic mechanism and suggest a strategy for PLR engineering.

    • Ying Xiao
    • , Kai Shao
    •  & Wansheng Chen

  • Article
    | Open Access

    Our structural understanding of class A penicillin binding proteins is incomplete due to the difficulty in their crystallization and the complexity of their substrates. Here, authors determine the structure of the 83 kDa class A PBP from Escherichia coli, PBP1b, using cryogenic electron microscopy and a styrene maleic acid anhydride membrane mimetic.

    • Nathanael A. Caveney
    • , Sean D. Workman
    •  & Natalie C. J. Strynadka

  • Article
    | Open Access

    Predicting RNA structure from sequence is challenging due to the relative sparsity of experimentally-determined RNA 3D structures for model training. Here, the authors propose a way to incorporate knowledge on interactions at the atomic and base–base level to refine the prediction of RNA structures.

    • Peng Xiong
    • , Ruibo Wu
    •  & Yaoqi Zhou

  • Article
    | Open Access

    The allosteric regulation of the bienzyme complex imidazole glycerol phosphate synthase (HisFH) remains to be elucidated. Here, the authors provide structural insights into the dynamic allosteric mechanism by which ligand binding to the cyclase and glutaminase active sites of HisFH regulate enzyme activation.

    • Jan Philip Wurm
    • , Sihyun Sung
    •  & Remco Sprangers

  • Article
    | Open Access

    HIV-1 integrase (IN) binds the host factor INI1/SMARCB1, which is required at multiple stages of HIV-1 replication. Here, the authors show that the same IN residues are involved in INI1 and RNA binding and in influencing particle morphogenesis and suggest that the IN-binding INI1 domain is structurally similar to HIV TAR RNA.

    • Updesh Dixit
    • , Savita Bhutoria
    •  & Ganjam V. Kalpana

  • Article
    | Open Access

    AIM2-ASC inflammasomes are filamentous signalling platforms that play a central role in host innate defence. Here, the authors present the filament cryo-EM structure of the inflammasome receptor AIM2, which is very similar to the adaptor ASC filament structure. By employing Rosetta and Molecular Dynamics simulations the authors provide further insights into the directionality and recognition mechanisms of the individual AIM2 and ASC filaments, which is further validated with biochemical and cellular experiments.

    • Mariusz Matyszewski
    • , Weili Zheng
    •  & Jungsan Sohn

  • Article
    | Open Access

    The MerR family of transcriptional regulators, such as EcmrR, activate promoters with a structure that is suboptimal for recognition by RNA polymerase holoenzyme. Structural insights into the EcmrR-dependent transcription process elucidate the mechanisms enabling optimal promoter recognition and transition from initiation to elongation.

    • Yang Yang
    • , Chang Liu
    •  & Bin Liu

  • Article
    | Open Access

    DNA polymerases are the key enzymes responsible for DNA replication and repair. Here the authors reveal through time-lapsed images of X-ray crystal structures that translocation precedes phosphodiester bond formation in the mechanism of DNA synthesis.

    • Nicholas Chim
    • , Roman A. Meza
    •  & John C. Chaput

  • Article
    | Open Access

    Antibodies against SARS-CoV-2 S protein can provide a treatment strategy for COVID-19. Here, Guo et al. provide the crystal structure of a SARS-CoV2 neutralizing antibody isolated from a convalescent patient and highlight the therapeutic efficacy in a rhesus monkey model of an engineered version with optimized pharmacokinetic and safety profile.

    • Yu Guo
    • , Lisu Huang
    •  & Zihe Rao

  • Article
    | Open Access

    Activation of cullin-RING ligases can be inhibited by targeting DCN1, but selective DCN1 inhibitors with in vivo activity are lacking. Here, the authors develop covalent DCN1 inhibitors that selectively and potently inhibit cullin-3 activation and downstream functions in cells and in mice.

    • Haibin Zhou
    • , Jianfeng Lu
    •  & Shaomeng Wang

  • Article
    | Open Access

    While SARS-CoV-2 S protein targeting monoclonal antibodies (mAbs) are well studied, little is known about N protein-targeting mAbs. Here, Kang et al. provide the crystal structure of the N protein RNA binding domain with a mAb derived from a convalescent patient and show that it compromises the N protein-induced complement hyperactivation.

    • Sisi Kang
    • , Mei Yang
    •  & Shoudeng Chen

  • Article
    | Open Access

    MAL and MyD88 are downstream adaptors of Toll-like receptors (TLR) and the MAL TIR domain forms filaments in vitro, which in turn nucleate the assembly of crystalline arrays of the MyD88 TIR domain. Here, the authors present the structure of these MyD88 TIR crystalline arrays solved by both microcrystal electron diffraction and serial femtosecond crystallography, and they show with mutagenesis experiments that MyD88 interface residues are important for TLR4 signaling in vivo.

    • Max T. B. Clabbers
    • , Susannah Holmes
    •  & Thomas Ve

  • Article
    | Open Access

    In some systems, a single protein comprising reverse transcriptase (RT), integrase and maturase enables concerted sequence integration and crRNA production. Here, analyses including the structure of a Cas6-RT-Cas1—Cas2 complex suggest coordination between all three active sites and capacity to acquire CRISPR sequences from RNA and DNA substrates.

    • Joy Y. Wang
    • , Christopher M. Hoel
    •  & Jennifer A. Doudna

  • Article
    | Open Access

    Flaviviruses use a ~70 nucleotide stem-loop structure called stem-loop A (SLA) at the 5’ end of the RNA genome as a promoter for RNA synthesis by the viral polymerase NS5. Here the authors describe the structures of dengue and Zika virus SLAs, identify the SLA-binding site on NS5, and propose models for how NS5 recognizes the RNA promoter.

    • Eunhye Lee
    • , Paul J. Bujalowski
    •  & Kyung H. Choi

  • Article
    | Open Access

    Initiation of HIV-1 reverse transcription occurs at the host tRNALys3, which forms a complex with the 5’ end of the HIV-1 viral RNA and reverse transcriptase (RT). Here, the authors present the 2.8 Å cryo-EM structure of a minimal HIV-1 RT–vRNA–tRNALys3 initiation complex (miniRTIC), and miniRTIC structures with the bound non-nucleoside reverse transcriptase inhibitors nevirapine and efavirenz at 3.1 and 2.9 Å resolution, respectively.

    • Betty Ha
    • , Kevin P. Larsen
    •  & Elisabetta Viani Puglisi

  • Article
    | Open Access

    Non-ribosomal peptide synthetases (NRPSs) are multi-modular enzymes assembling complex natural products. Here, the structures of a Thermobifida fusca NRPS condensation domain bound to the substrate-bearing peptidyl carrier protein (PCP) domain provide insight into the mechanisms of substrate selectivity and engagement within the catalytic pocket.

    • Thierry Izoré
    • , Y. T. Candace Ho
    •  & Max J. Cryle

  • Article
    | Open Access

    How histone modifications crosstalk with DNA methylation to regulate epigenomic patterning and genome stability in mammals remains elusive. Here, the authors show that DNA methyltransferase DNMT1 is a reader for histone H4K20 trimethylation via its BAH1 domain, which leads to optimal maintenance of DNA methylation at repetitive LINE-1 elements.

    • Wendan Ren
    • , Huitao Fan
    •  & Jikui Song

  • Article
    | Open Access

    The cyanophage S-2L incorporates 2-aminoadenine (Z) instead of adenine (A) in its genome. Here, the authors provide an explanation for the absence of A in S-2L genome by identifying and characterising functionally and structurally both the HD phosphohydrolase (datZ) that specifically cleaves dATP, and the sole DNA primase-polymerase of S-2L, nonspecific of dATP or dZTP.

    • Dariusz Czernecki
    • , Pierre Legrand
    •  & Marc Delarue

  • Article
    | Open Access

    The ER chaperone BiP is critical for the unfolded protein response and tightly regulated through reversible AMPylation by FICD, but the structural basis is unknown. Here the authors use thiol-reactive nucleotide derivatives to stabilize the transient FICD:BiP complex and determine its crystal structure.

    • Joel Fauser
    • , Burak Gulen
    •  & Aymelt Itzen

  • Article
    | Open Access

    The interaction between a GPCR, such as the vasopressin receptor-2 (V2R), and arrestin depends on the receptors’ phosphorylation pattern. Here authors use FRET and NMR to analyze the phosphorylation patterns of the V2R-arrestin complex and show that phospho-interactions are the key determinants of selective arrestin conformational states and correlated functions.

    • Qing-Tao He
    • , Peng Xiao
    •  & Xiao Yu

  • Article
    | Open Access

    The molecular mechanism of ubiquitin transfer from E1 to E2 enzymes is still unclear. By solving the crystal structure of a covalently trapped E1–E2–ubiquitin thioester mimetic, the authors identify two conformations of this complex which suggest an affinity switch mechanism for thioester transfer.

    • Lingmin Yuan
    • , Zongyang Lv
    •  & Shaun K. Olsen

  • Article
    | Open Access

    Acaryochloris marina photosystem I (PSI) contains chlorophyll d and absorbs light in the far-red region of the spectrum. The structure of A. marina PSI reaction center reveals several unusual features, including pheophytin as the primary electron acceptor.

    • Tasuku Hamaguchi
    • , Keisuke Kawakami
    •  & Yasuhiro Kashino

  • Article
    | Open Access

    The molecular architecture of α-Synuclein (α-Syn) inclusions, pathognomonic of various neurodegenerative disorders, remains unclear. Here, authors use cryo-electron tomography to image neuronal α-Syn inclusions in situ and find that inclusions consist of α-Syn fibrils intermixed with cellular organelles without interacting directly.

    • Victoria A. Trinkaus
    • , Irene Riera-Tur
    •  & Rubén Fernández-Busnadiego

  • Article
    | Open Access

    Mixed Lineage Kinase Domain-Like (MLKL) pseudokinase is phosphorylated by RIPK3 kinase prior to cell death by necroptosis. Here, the authors use monobodies that bind to the MLKL pseudokinase domain as tools, which allowed them to determine the crystal structures of the MLKL pseudokinase domain in two distinct conformations. By combining their structural data with cell signalling assays and MD simulations they provide evidence that endogenous MLKL preassociates with its upstream regulator RIPK3, and that MLKL disengages from RIPK3 following the induction of necroptosis.

    • Sarah E. Garnish
    • , Yanxiang Meng
    •  & James M. Murphy

  • Article
    | Open Access

    The intrinsically disordered acidic activation domain (AD) of the yeast transcription factor Gal4 acts through binding to the Med15 subunit of the Mediator complex. Here, the authors show that Gal4 interacts with Med15 through an identical fuzzy binding mechanism as Gcn4 AD, which has a different sequence, revealing a common sequence-independent mechanism for AD-Mediator binding. In contrast, Gal4 AD binds to the Gal80 repressor as a structured polypeptide, which strongly suggests that the structured binding partner dictates the type of protein–protein interaction for an intrinsically disordered protein.

    • Lisa M. Tuttle
    • , Derek Pacheco
    •  & Rachel E. Klevit

  • Article
    | Open Access

    The Drosophila dopamine transporter (dDAT) is a catecholamine neurotransmitter transporter that resembles the human norepinephrine transporter (hNET). Here the authors report X-ray structures of the dDAT in substrate-free form, norepinephrine-bound form and dDAT bound to commonly prescribed chronic pain inhibitors duloxetine, milnacipran and tramadol and shed light on the structural basis of norepinephrine recognition and transport inhibition in neurotransmitter transporters.

    • Shabareesh Pidathala
    • , Aditya Kumar Mallela
    •  & Aravind Penmatsa

  • Article
    | Open Access

    As part of two-component systems, diguanylate cyclases (DGCs) are activated by phosphorylation. Structural and computational analyses of DgcR, a model DGC, reveal the phosphorylation-induced conformational changes and the activation mechanism likely shared by many DGCs with N-terminal coiled-coil linkers.

    • Raphael D. Teixeira
    • , Fabian Holzschuh
    •  & Tilman Schirmer

  • Article
    | Open Access

    KIR2DL2 and KIR2DL3 are two inhibitory members of the killer-cell immunoglobulin-like receptors (KIR) family that share a common HLA-I preference in binding HLA from the C1 group. However, it is still unclear to what extent binding and function is equivalent between KIR2DL2 and 2DL3. Here, the authors present the crystal structures of KIR2DL2 and 2DL3 in complex with HLA-C*07:02 and observe differences in HLA-C recognition between KIR2DL2 and 2DL3, which correlates with differences in HLA-C binding preference as they show with mutagenesis and binding studies.

    • Shoeib Moradi
    • , Sanda Stankovic
    •  & Julian P. Vivian

  • Article
    | Open Access

    The glutamine fructose-6-phosphate amidotransferase 1 (GFAT-1) is the rate-limiting enzyme in the hexosamine pathway producing uridine 5’-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc), an essential glycosylation precursor. Here, the authors dissect the mechanisms of GFAT-1 regulation by protein kinase A (PKA)-mediated phosphorylation.

    • Sabine Ruegenberg
    • , Felix A. M. C. Mayr
    •  & Martin S. Denzel

  • Article
    | Open Access

    Structural and functional characterization of the full-length TRPV1 channel from the thirteen-lined ground squirrel reveal the architecture of the extracellular cap domain and the intracellular C-terminus, and suggest a role of the cap domain in TRPV1 conductance and ion selectivity.

    • Kirill D. Nadezhdin
    • , Arthur Neuberger
    •  & Alexander I. Sobolevsky

  • Article
    | Open Access

    Microbial oxidoreductases are key in biomass breakdown. Here, the authors expand the specificity and redox scope within fungal auxiliary activity 7 family (AA7) enzymes and show that AA7 oligosaccharide dehydrogenases can directly fuel cellulose degradation by lytic polysaccharide monooxygenases.

    • Majid Haddad Momeni
    • , Folmer Fredslund
    •  & Maher Abou Hachem

  • Article
    | Open Access

    Histamine receptors are effective targets for allergy treatments and antihistamines are the first choice of many allergic disorders, but the exact mechanism of agonist binding and receptor activation remain unknown. Here, the authors present the cryo-EM structure of histamine-bound H1R/Gq complex and propose a mechanism of ligand induced receptor activation.

    • Ruixue Xia
    • , Na Wang
    •  & Yuanzheng He

  • Article
    | Open Access

    Human manganese superoxide dismutase (MnSOD) is an oxidoreductase that uses concerted proton and electron transfers to reduce the levels of superoxide radicals in mitochondria, but mechanistic insights into this process are limited. Here, the authors report neutron crystal structures of Mn3+SOD and Mn2+SOD, revealing changes in the protonation states of key residues in the enzyme active site during the redox cycle.

    • Jahaun Azadmanesh
    • , William E. Lutz
    •  & Gloria E. O. Borgstahl

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