Structural biology, biochemistry and biophysics

Structural insights into an atypical secretory pathway kinase crucial for Toxoplasma gondii invasion

Host cell invasion by Toxoplasma gondii depends on the heavily phosphorylated RON complex, but the relevance and regulation of these modifications are not understood. Here, the authors identify the kinase RON13 as a key virulence factor, determine its structure and…

Gaëlle Lentini,
Rouaa Ben Chaabene ⋯
Dominique Soldati-Favre

Article | Open Access | 18 Jun 2021 | Nature Communications

Tight docking of membranes before fusion represents a metastable state with unique properties

Proteins need to overcome energy barriers to induce intermediate steps in membrane fusion. Using lipid vesicles in which progression to hemifusion is arrested, the authors show that the metastable intermediate is enhanced by divalent cations and is characterized by…

Agata Witkowska,
Leonard P. Heinz ⋯
Reinhard Jahn

Article | Open Access | 14 Jun 2021 | Nature Communications

Ultrafast coherent motion and helix rearrangement of homodimeric hemoglobin visualized with femtosecond X-ray solution scattering

Femtosecond time-resolved X-ray solution scattering (fs-TRXSS) measurements provide information on the structural dynamics of proteins in solution. Here, the authors present a structure refinement method for the analysis of fs-TRXSS data and use it to characterise…

Yunbeom Lee,
Jong Goo Kim ⋯
Hyotcherl Ihee

Article | Open Access | 16 Jun 2021 | Nature Communications

Machine learning differentiates enzymatic and non-enzymatic metals in proteins

The authors generate the largest structural dataset of enzymatic and non-enzymatic metalloprotein sites to date. They use this dataset to train a decision-tree ensemble machine learning algorithm that allows them to distinguish between catalytic and non-catalytic…

Ryan Feehan,
Meghan W. Franklin &
Joanna S. G. Slusky

Article | Open Access | 17 Jun 2021 | Nature Communications

Large Stokes shift fluorescence activation in an RNA aptamer by intermolecular proton transfer to guanine

Fluorogenic RNA aptamers such as Chili display strong fluorescence enhancement upon aptamer–ligand complex formation. Here, the authors provide insights into the mechanism of fluorescence activation of Chili by solving the crystal structures of Chili with its bound…

Mateusz Mieczkowski,
Christian Steinmetzger ⋯
Claudia Höbartner

Article | Open Access | 10 Jun 2021 | Nature Communications

Proline/arginine dipeptide repeat polymers derail protein folding in amyotrophic lateral sclerosis

The most frequent cause of familial Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are hexanucleotide repeat expansions in the non-coding region of the C9ORF72 gene that are translated into five dipeptide repeat (DPR) proteins. Here, the…

Maria Babu,
Filippo Favretto ⋯
Markus Zweckstetter

Article | Open Access | 7 Jun 2021 | Nature Communications

Assessment of protein–protein interfaces in cryo-EM derived assemblies

Here, the authors present Protein Interface-score (PI-score), a machine learning-based metric that has been trained on protein–protein interfaces’ features from high-resolution crystal structures. They use the PI-score to evaluate the protein–protein interfaces in…

Sony Malhotra,
Agnel Praveen Joseph ⋯
Maya Topf

Article | Open Access | 7 Jun 2021 | Nature Communications

Structures of the human LONP1 protease reveal regulatory steps involved in protease activation

The human mitochondrial protease LONP1 is an AAA+ ATP-dependent quality control protease. Here, the authors present the cryo-EM structures of human LONP1 in three distinct states and provide insights into the mechanism and regulation of this important protease.

Mia Shin,
Edmond R. Watson ⋯
Gabriel C. Lander

Article | Open Access | 28 May 2021 | Nature Communications

Cryo-EM structure of TFIIH/Rad4–Rad23–Rad33 in damaged DNA opening in nucleotide excision repair

The conserved eukaryotic nucleotide excision repair (NER) pathway protects the genome from a wide variety of environmentally induced DNA lesions. Here, the authors provide insights into how NER is initiated on lesions by determining the cryo-EM structure of the…

Trevor van Eeuwen,
Yoonjung Shim ⋯
Kenji Murakami

Article | Open Access | 7 Jun 2021 | Nature Communications

Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix

Clostridioides difficile adenine methyltransferase A (CamA) is required for the sporulation and colonization of the pathogen that causes gastrointestinal infections. Here, the authors characterise CamA kinetically and present its crystal structure bound to the DNA…

Jujun Zhou,
John R. Horton ⋯
Xiaodong Cheng

Article | Open Access | 8 Jun 2021 | Nature Communications

Sugar phosphate activation of the stress sensor eIF2B

The activity of translation initiation factor eIF2B is known to be modulated through stress-responsive phosphorylation of its substrate eIF2. Here, the authors uncover the regulation of eIF2B by the binding of sugar phosphates, suggesting a link between nutrient…

Qi Hao,
Jin-Mi Heo ⋯
Carmela Sidrauski

Article | Open Access | 8 Jun 2021 | Nature Communications

Structural insight on assembly-line catalysis in terpene biosynthesis

Substrate channeling can improve biosynthetic efficiency and has been implicated in the reactions of fusicoccadiene synthase. Here, the authors analyze this bifunctional enzyme complex by cryoEM, cross-linking MS and integrative modeling, providing structural…

Jacque L. Faylo,
Trevor van Eeuwen ⋯
David W. Christianson

Article | Open Access | 9 Jun 2021 | Nature Communications

Intracellular artificial supramolecules based on de novo designed Y15 peptides

Self-assembling peptides (SAPs) can be used to build biomaterials, but genetically encoded SAPs have rarely been used as building blocks in cells. Here, the authors design a SAP that can be genetically fused to target proteins to induce their intracellular…

Takayuki Miki,
Taichi Nakai ⋯
Hisakazu Mihara

Article | Open Access | 7 Jun 2021 | Nature Communications

Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer

Inositol hexakisphosphate (IP6) is a known assembly cofactor for HIV-1. Here, the authors show the role of IP6 in the assembly of the Rous sarcoma virus (RSV). Reported cryo-ET structures of mature capsid-like particles (CLPs) suggest that IP6 modulates the…

Martin Obr,
Clifton L. Ricana ⋯
Robert A. Dick

Article | Open Access | 28 May 2021 | Nature Communications

Cryo-EM structure of cortical microtubules from human parasite Toxoplasma gondii identifies their microtubule inner proteins

Cortical microtubules (MTs) in Apicomplexa are specialized MTs involved in maintaining the parasite’s shape and are, as such, unusually stable. Here, cryo-EM analysis of cortical MTs from Toxoplasma gondii offers insight into the mechanism of their stabilization by…

Xiangli Wang,
Yong Fu ⋯
Rui Zhang

Article | Open Access | 24 May 2021 | Nature Communications

Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions

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…

Xiaopan Gao,
Kaixiang Zhu ⋯
Sheng Cui

Article | Open Access | 14 May 2021 | Nature Communications

Inhibition mechanism of SARS-CoV-2 main protease by ebselen and its derivatives

Ebselen is an organoselenium drug that inhibits the SARS-CoV-2 main protease (Mpro). Here, the authors co-crystallised Mpro with ebselen and an ebselen derivative and observed an enzyme bound organoselenium covalent adduct in the crystal structures, which was also…

Kangsa Amporndanai,
Xiaoli Meng ⋯
S. Samar Hasnain

Article | Open Access | 24 May 2021 | Nature Communications

Cryo-EM structure of the mature and infective Mayaro virus at 4.4 Å resolution reveals features of arthritogenic alphaviruses

Mayaro virus (MAYV) is an emerging arbovirus in Central and South America that is transmitted by mosquitoes and causes arthritogenic disease. Here, the authors present the 4.4 Å resolution cryo-EM structure of MAYV and describe specific features of the virus, which…

Helder V. Ribeiro-Filho,
Lais D. Coimbra ⋯
Rafael Elias Marques

Article | Open Access | 24 May 2021 | Nature Communications

TAPBPR promotes antigen loading on MHC-I molecules using a peptide trap

The molecular chaperones tapasin and TAPBPR play important roles in defining the repertoire of peptides displayed by MHC class I. Here, the authors combine NMR, ITC, fluorescence polarization measurements and deep mutational scanning analyses to reveal a peptide…

Andrew C. McShan,
Christine A. Devlin ⋯
Nikolaos G. Sgourakis

Article | Open Access | 26 May 2021 | Nature Communications

Structural basis of substrate recognition and thermal protection by a small heat shock protein

Structural insights into the small heat shock proteins (sHsps) complexes with their substrates are sparse. Here, cryo-EM structure of a plastid sHsp, Hsp21, in complex with a bona fide substrate 1-deoxy-D-xylulose 5-phosphate synthase (DXPS), suggests the…

Chuanyang Yu,
Stephen King Pong Leung ⋯
Wilson Chun Yu Lau

Article | Open Access | 21 May 2021 | Nature Communications

Single-cell lipidomics with high structural specificity by mass spectrometry

Analyzing the lipidomes of single cells remains a challenge. Here, the authors present a strategy to identify class, fatty acyl-chain, C=C locations and sn-positions of lipids in single cells, and use their method to identify individual gefitinib-resistant cells in…

Zishuai Li,
Simin Cheng ⋯
Zheng Ouyang

Article | Open Access | 17 May 2021 | Nature Communications

MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography

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…

Max T. B. Clabbers,
Susannah Holmes ⋯
Thomas Ve

Article | Open Access | 10 May 2021 | Nature Communications

High-resolution view of HIV-1 reverse transcriptase initiation complexes and inhibition by NNRTI drugs

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…

Betty Ha,
Kevin P. Larsen ⋯
Elisabetta Viani Puglisi

Article | Open Access | 4 May 2021 | Nature Communications

Structural coordination between active sites of a CRISPR reverse transcriptase-integrase complex

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…

Joy Y. Wang,
Christopher M. Hoel ⋯
Jennifer A. Doudna

Article | Open Access | 6 May 2021 | Nature Communications

Structures of a non-ribosomal peptide synthetase condensation domain suggest the basis of substrate selectivity

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…

Thierry Izoré,
Y. T. Candace Ho ⋯
Max J. Cryle

Article | Open Access | 4 May 2021 | Nature Communications

Cryo-EM structures of an insecticidal Bt toxin reveal its mechanism of action on the membrane

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…

Matthew J. Byrne,
Matthew G. Iadanza ⋯
Rebecca F. Thompson

Article | Open Access | 14 May 2021 | Nature Communications

CryoEM structure of the antibacterial target PBP1b at 3.3 Å resolution

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,…

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

Article | Open Access | 13 May 2021 | Nature Communications

Conformational rearrangement of the NMDA receptor amino-terminal domain during activation and allosteric modulation

N-Methyl-D-aspartate receptors (NMDARs) activation involves closure of the GluN1 and GluN2 subunit ligand binding domains, which is regulated allosterically by the amino-terminal domain (ATD). Here, smFRET, used to monitor conformational rearrangements of the NMDAR…

Vojtech Vyklicky,
Cherise Stanley ⋯
Ehud Y. Isacoff

Article | Open Access | 11 May 2021 | Nature Communications

How cyanophage S-2L rejects adenine and incorporates 2-aminoadenine to saturate hydrogen bonding in its DNA

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)…

Dariusz Czernecki,
Pierre Legrand ⋯
Marc Delarue

Article | Open Access | 23 Apr 2021 | Nature Communications

Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD

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…

Joel Fauser,
Burak Gulen ⋯
Aymelt Itzen

Article | Open Access | 23 Apr 2021 | Nature Communications

Reconstitution of contractile actomyosin rings in vesicles

Cytoskeletal networks support and direct cell shape and guide intercellular transport, but relatively little is understood about the self-organization of cytoskeletal components on the scale of an entire cell. Here, authors use an in vitro system and observe the…

Thomas Litschel,
Charlotte F. Kelley ⋯
Petra Schwille

Article | Open Access | 15 Apr 2021 | Nature Communications

Histone dynamics mediate DNA unwrapping and sliding in nucleosomes

Nucleosomes tightly wrap ~147 DNA base pairs around an octamer of histone proteins, but how nucleosome structural dynamics affect genome functioning is not completely clear. Here authors employ all-atom molecular dynamics simulations of nucleosome core particles and…

Grigoriy A. Armeev,
Anastasiia S. Kniazeva ⋯
Alexey K. Shaytan

Article | Open Access | 22 Apr 2021 | Nature Communications

FtsZ treadmilling is essential for Z-ring condensation and septal constriction initiation in Bacillus subtilis cell division

Bacterial cell division by cell wall synthesis proteins is guided by treadmilling filaments of the cytoskeleton protein FtsZ. Here authors use nanofabrication, advanced microscopy, and microfluidics to resolve the function of FtsZ treadmilling in the Gram-positive model organism Bacillus subtilis.

Kevin D. Whitley,
Calum Jukes ⋯
Séamus Holden

Article | Open Access | 27 Apr 2021 | Nature Communications

Force-FAK signaling coupling at individual focal adhesions coordinates mechanosensing and microtissue repair

How adhesive forces are transduced and integrated into biochemical signals at focal adhesions (FAs) is poorly understood. Here authors show that force- FAK signaling coupling coordinates cell migration and tissue-scale forces to promote microtissue repair.

Dennis W. Zhou,
Marc A. Fernández-Yagüe ⋯
Andrés J. García

Article | Open Access | 21 Apr 2021 | Nature Communications

VESPER: global and local cryo-EM map alignment using local density vectors

Here, the authors present VESPER, a program for EM density map search and alignment. Using benchmark datasets, they demonstrate that VESPER performs accurate global and local alignments and comparisons of EM maps.

Xusi Han,
Genki Terashi ⋯
Daisuke Kihara

Article | Open Access | 7 Apr 2021 | Nature Communications

A self-organized synthetic morphogenic liposome responds with shape changes to local light cues

The authors generated a Synthetic Morphogenic Membrane System by encapsulating a dynamic microtubule aster and a light-inducible signaling system driven by GTP/ATP chemical potential into cell-sized liposomes. This reconstitution of artificial proto-cells reveals…

Konstantin Gavriljuk,
Bruno Scocozza ⋯
Philippe I. H. Bastiaens

Article | Open Access | 9 Mar 2021 | Nature Communications

Robust nucleation control via crisscross polymerization of highly coordinated DNA slats

For programmable DNA self-assembly, it is desirable to suppress spontaneous nucleation to enable all-or-nothing assembly of nanostructures far larger than a single DNA origami. Here the authors introduce crisscross polymerization of elongated slat monomers that…

Dionis Minev,
Christopher M. Wintersinger ⋯
William M. Shih

Article | Open Access | 19 Mar 2021 | Nature Communications

In situ architecture of neuronal α-Synuclein inclusions

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…

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

Article | Open Access | 14 Apr 2021 | Nature Communications

Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis

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…

Sarah E. Garnish,
Yanxiang Meng ⋯
James M. Murphy

Article | Open Access | 13 Apr 2021 | Nature Communications

The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones

Tissue-specific differences in protein folding capacities are poorly understood. Here, the authors show that the human chaperone system consists of ubiquitous core chaperones and tissue-specific variable chaperones, perturbation of which leads to tissue-specific phenotypes.

Netta Shemesh,
Juman Jubran ⋯
Esti Yeger-Lotem

Article | Open Access | 12 Apr 2021 | Nature Communications

Extracellular cap domain is an essential component of the TRPV1 gating mechanism

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 | 12 Apr 2021 | Nature Communications

Mapping specificity, cleavage entropy, allosteric changes and substrates of blood proteases in a high-throughput screen

Characterizing proteases in their native environment is still challenging. Here, the authors develop a proteomics workflow for analyzing protease-specific peptides from cell lysates in 96-well format, providing mechanistic insights into blood proteases and enabling…

Federico Uliana,
Matej Vizovišek ⋯
Ruedi Aebersold

Article | Open Access | 16 Mar 2021 | Nature Communications

Beam image-shift accelerated data acquisition for near-atomic resolution single-particle cryo-electron tomography

Tomographic reconstructions of cryopreserved specimens enable in-situ structural studies. Here, the authors present the beam image-shift electron cryo-tomography (BISECT) approach that accelerates data collection speed and improves the map resolution compared to…

Jonathan Bouvette,
Hsuan-Fu Liu ⋯
Alberto Bartesaghi

Article | Open Access | 30 Mar 2021 | Nature Communications

Asymmetric opening of the homopentameric 5-HT3A serotonin receptor in lipid bilayers

Pentameric ligand-gated ion channels (pLGICs) are key players in neurotransmission and have been shown to be modulated by the lipid environment, however the underlying mechanism is not well understood. Here, the authors report structures of the pLGIC 5-HT3A…

Yingyi Zhang,
Patricia M. Dijkman ⋯
Mikhail Kudryashev

Article | Open Access | 16 Feb 2021 | Nature Communications

Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions

Elucidating the molecular driving forces underlying liquid–liquid phase separation is a key objective for understanding biological function and malfunction. Here the authors show that a wide range of cellular proteins, including FUS, TDP-43, Brd4, Sox2, and Annexin…

Georg Krainer,
Timothy J. Welsh ⋯
Tuomas P. J. Knowles

Article | Open Access | 17 Feb 2021 | Nature Communications

The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA

SARS-CoV-2 nucleocapsid (N) protein is responsible for viral genome packaging. Here the authors employ single-molecule spectroscopy with all-atom simulations to provide the molecular details of N protein and show that it undergoes phase separation with RNA.

Jasmine Cubuk,
Jhullian J. Alston ⋯
Alex S. Holehouse

Article | Open Access | 29 Mar 2021 | Nature Communications

Structure and binding properties of Pangolin-CoV spike glycoprotein inform the evolution of SARS-CoV-2

It has been suggested that pangolin coronaviruses may be the origin of SARS-CoV-2. Here the authors show that the Pangolin-CoV spike is structurally closely related to the closed form of SARS-CoV-2 spike and exhibits similar binding properties to human and pangolin…

Antoni G. Wrobel,
Donald J. Benton ⋯
Steven J. Gamblin

Article | Open Access | 5 Feb 2021 | Nature Communications

Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution

The spike glycoprotein in coronaviruses is a key viral protein for cross-species transmission and infection. Here, the authors present the cryo-EM structures of the spike ectodomains from bat and pangolin coronaviruses, compare them with the available SARS-CoV-2…

Shuyuan Zhang,
Shuyuan Qiao ⋯
Xinquan Wang

Article | Open Access | 11 Mar 2021 | Nature Communications

Cryo-EM structure of amyloid fibrils formed by the entire low complexity domain of TDP-43

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) patients have brain deposits with amyloid-like aggregates from large C-terminal fragments of the transactive response DNA-binding protein of 43 kDa (TDP-43). Here, the authors present…

Qiuye Li,
W. Michael Babinchak &
Witold K. Surewicz

Article | Open Access | 12 Mar 2021 | Nature Communications

The amyloid structure of mouse RIPK3 (receptor interacting protein kinase 3) in cell necroptosis

Receptor Interacting Protein Kinase 3 (RIPK3) has a key role in TNF-induced necroptosis. Here, the authors combine solid state NMR measurements, MD simulations and cell based assays to characterize mouse RIPK3 and they present the structure of the RIPK3 amyloid core.

Xia-lian Wu,
Hong Hu ⋯
Jun-xia Lu

Article | Open Access | 12 Mar 2021 | Nature Communications

Structural biology, biochemistry and biophysics

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