NMR spectroscopy

  • Article
    | Open Access

    Here, the authors combine 3D printing and liquid metal filling techniques to fabricate customised probeheads for magnetic resonance experiments. They demonstrate in situ electrochemical nuclear magnetic resonance analysis, reaction monitoring with continues-flow separation and small-sample imaging.

    • Junyao Xie
    • , Xueqiu You
    •  & Zhong Chen
  • Article
    | Open Access

    Bacteriophages of the Siphoviridae family have a long, flexible, non-contractile tail that has been difficult to characterize structurally. Here, the authors present the atomic structure of the tail tube of one of these phages, showing a hollow flexible tube formed by hexameric rings stacked by flexible linkers.

    • Maximilian Zinke
    • , Katrin A. A. Sachowsky
    •  & Adam Lange
  • Article
    | Open Access

    The low-complexity (LC) domain mediates liquid-liquid phase separation and fibril formation of the RNA-binding protein FUS (FUsed in Sarcoma). Here, the authors combine cryo-EM, solid-state NMR measurements and MD simulations to structurally characterise the fibrils formed by the C-terminal half of the FUS LC domain and discuss stabilizing interactions within the fibril core.

    • Myungwoon Lee
    • , Ujjayini Ghosh
    •  & Robert Tycko
  • Article
    | Open Access

    So far only a few compounds have been reported as splicing modulators. Here, the authors combine high-throughput screening, chemical synthesis, NMR, X-ray crystallography with functional studies and develop phenothiazines as inhibitors for the U2AF Homology Motif (UHM) domains of proteins that regulate splicing and show that they inhibit early spliceosome assembly on pre-mRNA substrates in vitro.

    • Pravin Kumar Ankush Jagtap
    • , Tomáš Kubelka
    •  & Michael Sattler
  • Article
    | Open Access

    As protein synthesis takes place, newly synthesized polypeptide chain passes through the ribosomal exit tunnel, which can accommodate up to 70 residues in the case of a helical peptide. Here the authors show that oxidation of cysteine residues in the nascent chain can occur within the ribosome exit tunnel, where sufficient space exists for the formation of disulfide bonds.

    • Linda Schulte
    • , Jiafei Mao
    •  & Harald Schwalbe
  • Article
    | Open Access

    The structure and dynamics of large proteins and complexes can be studied by methyl-NMR but resonance assignment is still challenging. Here, the authors present a NMR method that leverages optimal control pulse design to unambiguously distinguish between Leu and Val using a simple 2D HMQC experiment and they apply it to several proteins including Cas9, interleukin, and human translation initiation factor eIF4a.

    • Soumya P. Behera
    • , Abhinav Dubey
    •  & Haribabu Arthanari
  • Article
    | Open Access

    β-phosphoglucomutase (βPGM) from Lactococcus lactis is a phosphoryl transfer enzyme required for catabolism of trehalose and maltose. Coupled analyses of multiple βPGM structures and enzymatic activity lead to the proposal of allomorphy — a post-translational mechanism controlling enzyme activity.

    • Henry P. Wood
    • , F. Aaron Cruz-Navarrete
    •  & Jonathan P. Waltho
  • Article
    | Open Access

    Determining dynamic ensembles of biomolecules is still challenging. Here the authors present an approach for rapid RNA ensemble determination that combines RNA structure prediction tools and NMR residual dipolar coupling data and use it to determine atomistic ensemble models for a variety of RNAs.

    • Honglue Shi
    • , Atul Rangadurai
    •  & Hashim M. Al-Hashimi
  • Article
    | Open Access

    Here, the authors present an approach that enhances the sensitivity of basic 2D biomolecular NMR experiments like NOESY and TOCSY, when carried out in polysaccharides, proteins and nucleic acids. This method combines principles associated to quantum Anti-Zeno Effects and advanced data acquisition methods based on Hadamard multiplexing.

    • Mihajlo Novakovic
    • , Ēriks Kupče
    •  & Lucio Frydman
  • Article
    | Open Access

    Potassium ion channels control K+ permeation across cell membranes and mutations that cause cardiovascular and neural diseases are known. Here, the authors perform NMR measurements with the prototypical K+ channel from Streptomyces lividans, KcsA and characterise the effects of disease causing mutations on the conformational dynamics of K+ channels in a physiological solution environment.

    • Yuta Iwahashi
    • , Yuki Toyama
    •  & Ichio Shimada
  • Article
    | Open Access

    VARP is bound to endosomes and functions as a protein:protein interaction platform. Here, the authors present the NMR structure of the complex between the retromer subunit VPS29 and a VARP Zn-fingernail microdomain that is structurally distinct from Zn-fingers and further show that mutations, which abolish VPS29:VARP binding, inhibit trafficking from endosomes to the cell surface.

    • Harriet Crawley-Snowdon
    • , Ji-Chun Yang
    •  & David J. Owen
  • Article
    | Open Access

    Neisseria meningitidis capsular polysaccharide (CPS) is a major virulence factor and vaccine formulations against Neisseria meningitidis serogroup A (NmA) contain O-acetylated CPS. Here, the authors provide mechanistic insights into CPS O-acetylation in NmA by determining the crystal structure of the O-acetyltransferase CsaC and NMR measurements further reveal that the CsaC-mediated reaction is regioselective for O3 and that the O4 modification results from spontaneous O-acetyl migration.

    • Timm Fiebig
    • , Johannes T. Cramer
    •  & Martina Mühlenhoff
  • Article
    | Open Access

    Determination of 3D molecular structures remains challenging for natural products or organic compounds available in minute amounts. Here, the authors determine the structure of complex molecules, including few micrograms of briarane B-3 isolated from Briareum asbestinums, through measurement of 1H residual chemical shift anisotropy.

    • Nilamoni Nath
    • , Juan Carlos Fuentes-Monteverde
    •  & Christian Griesinger
  • Article
    | Open Access

    S. cerevisiae TBP associated factor 14 (Taf14) is a transcriptional regulator that interacts with multiple nuclear complexes. Here, the authors report that the extra-terminal domain of Taf14 (Taf14ET) recognizes a common motif in various transcriptional coactivator proteins and they solve the NMR structure of Taf14ET bound the ET-binding motif of Sth1, the catalytic subunit of the RSC (Remodel the Structure of Chromatin) complex, and furthermore show that Taf14ET undergoes liquid-liquid phase separation, which is enhanced by Taf14 interaction partners.

    • Guochao Chen
    • , Duo Wang
    •  & Yong Chen
  • Article
    | Open Access

    The TRPV1 ion channel is a heat-sensing receptor that is also activated by vanilloid compounds, but the molecular underpinnings of thermosensing have remained elusive. Here authors use in solution NMR on the isolated human TRPV1 S1-S4 domain and show that this domain undergoes a non-denaturing temperature-dependent transition with a high thermosensitivity.

    • Minjoo Kim
    • , Nicholas J. Sisco
    •  & Wade D. Van Horn
  • Article
    | Open Access

    Human Histone Deacetylases (HDACs) regulate gene expression and are important drug targets. Here, the authors combine NMR measurements, enzymatic assays and molecular dynamics simulations and show that HDAC8 samples a catalytically active and an inactive state and further demonstrate that mutations and ligand binding alter the populations of the two states, which is of interest for inhibitor design.

    • Nicolas D. Werbeck
    • , Vaibhav Kumar Shukla
    •  & D. Flemming Hansen
  • Article
    | Open Access

    Avian influenza polymerase undergoes host adaptation in order to efficiently replicate in human cells. Here, the authors use NMR spectroscopy and quantitative ensemble modelling to describe the highly dynamic assemblies formed by the human-adapted or avian-adapted C-terminal domains with the respective ANP32A host proteins.

    • Aldo R. Camacho-Zarco
    • , Sissy Kalayil
    •  & Martin Blackledge
  • Article
    | Open Access

    Mitochondrial apoptosis is controlled by BCL2 family proteins, and the BH3-only proteins often act as sensors that transmit apoptotic signals. Here the authors show how the BH3-only proteins BMF and HRK can directly activate the BCL2 protein BAK and interact with BAK through an alternative binding groove.

    • Kaiqin Ye
    • , Wei X. Meng
    •  & Haiming Dai
  • Article
    | Open Access

    Analysis of exchange processes is time consuming by two-dimensional exchange NMR spectroscopy. Here the authors demonstrate a single-scan ultrafast Laplace NMR approach based on spatial encoding to measure molecular diffusion, with an increase by a factor six in the sensitivity per unit time.

    • Otto Mankinen
    • , Vladimir V. Zhivonitko
    •  & Ville-Veikko Telkki
  • Article
    | Open Access

    Phosphorylation of eIF4E binding proteins (4E-BPs) controls their folding and regulates cap-dependent translation. Here, the authors show that phosphorylation of the C-terminal disordered region stabilizes the non-cooperatively folded 4E-BP domain to an eIF4E binding-incompatible state to control translation.

    • Jennifer E. Dawson
    • , Alaji Bah
    •  & Julie D. Forman-Kay
  • Article
    | Open Access

    Formation of amyloid-beta (Aβ) oligomer pores in the membrane of neurons has been proposed to explain neurotoxicity in Alzheimer´s disease. Here authors present the 3D- structure of an Aβ oligomer formed in a membrane mimicking environment and observe that Aβ tetramers and octamers inserted into lipid bilayers as well-defined pores.

    • Sonia Ciudad
    • , Eduard Puig
    •  & Natàlia Carulla
  • Article
    | Open Access

    The natural antibiotic teixobactin kills bacteria by direct binding to their cognate cell wall precursors (Lipid II and III). Here authors use solid-state NMR to reveal the native binding mode of teixobactins and show that teixobactins only weakly bind to Lipid II in anionic cellular membranes.

    • Rhythm Shukla
    • , João Medeiros-Silva
    •  & Markus Weingarth
  • Article
    | Open Access

    In Parkinson’s disease (PD) the monomeric protein alpha-synuclein (aSyn) misfolds and aggregates into insoluble fibrils. Here the authors use NMR measurements and hydrogen–deuterium exchange mass spectrometry and find that the more solvent exposed the N-terminus of aSyn is, the more aggregation prone its conformation becomes, and further show how PD mutations and post translational modifications influence the extent of the N-terminus solvent exposure.

    • Amberley D. Stephens
    • , Maria Zacharopoulou
    •  & Gabriele S. Kaminski Schierle
  • Article
    | Open Access

    HIV-1 envelope glycoprotein (Env) mediates the fusion of viral and target cell membranes and is a major target for HIV vaccine development. Here, the authors determine the NMR structure of a bicelle incorporated Env segment comprising the transmembrane domain (TMD) and a portion of the cytoplasmic tail (CT), and show that the CT folds into membrane attached amphipathic helices that wrap around the TMD thereby forming a support baseplate for the rest of Env, and they also provide insights into the dynamic coupling across the TMD between the ectodomain and CT.

    • Alessandro Piai
    • , Qingshan Fu
    •  & James J. Chou
  • Article
    | Open Access

    Understanding the solid–electrolyte interphase (SEI) is key to developing safe dendrite-free lithium batteries. Here, by exploiting the electrons in lithium metal to selectively hyperpolarise the NMR signals, the authors reveal the chemistry and spatial distribution of species at the metal–SEI interface.

    • Michael A. Hope
    • , Bernardine L. D. Rinkel
    •  & Clare P. Grey
  • Article
    | Open Access

    The chaperone Hsp90 uses the free energy from ATP hydrolysis to control the folding of client proteins in eukaryotic cells. Here the authors provide mechanistic insights into how its catalytic activity is coupled to conformational changes by combining large-scale molecular simulations with NMR, FRET and SAXS experiments.

    • Sophie L. Mader
    • , Abraham Lopez
    •  & Ville R. I. Kaila
  • Article
    | Open Access

    Human ubiquitin E3 ligase E6AP contains a Zn-binding AZUL domain. Here the authors identify and name RAZUL, a domain in proteasome substrate receptor hRpn10 that binds AZUL, recruiting E6AP to proteasomes, and they present the NMR structure of the RAZUL:AZUL complex, which forms an intermolecular 4-helix bundle.

    • Gwen R. Buel
    • , Xiang Chen
    •  & Kylie J. Walters
  • Article
    | Open Access

    The detection of topological states is restricted to limited experimental tools. Here, the authors apply broadband solid-state 125Te nuclear magnetic resonance on Bi2Te3 nanoplatelets uncovering signals distinguishing edge Dirac electrons and bulk electrons.

    • Wassilios Papawassiliou
    • , Aleksander Jaworski
    •  & Georgios Papavassiliou
  • Article
    | Open Access

    Galectin-3 consists of an unstructured N-terminal domain (NTD) and a structured carbohydrate-recognition domain and agglutinates neutrophils and glycosylated molecules in the extracellular milieu. Here the authors combine biophysical and biochemical experiments with NMR measurements and show that the galectin-3 NTD undergoes liquid-liquid phase separation (LLPS) and agglutinates other molecules through this process.

    • Yi-Ping Chiu
    • , Yung-Chen Sun
    •  & Jie-rong Huang
  • Article
    | Open Access

    The movement of cytoplasmic dynein on microtubule tracks is coordinated by the microtubule-binding domain (MTBD) and the ATPase domain via a coiled-coil stalk. Here authors use NMR and cryo-EM and suggest that the communication between the ATPase-domain and MTBD is achieved by sliding of the stalk α-helix by a half-turn or one-turn.

    • Noritaka Nishida
    • , Yuta Komori
    •  & Masahide Kikkawa
  • Article
    | Open Access

    Structural studies of nuclear receptor transcription factors revealed that nearly all nuclear receptors share a conserved helix 12 dependent transcriptional activation mechanism. Here the authors present two crystal structures of peroxisome proliferator-activated receptor gamma (PPARγ) in an inverse agonist/corepressor-bound transcriptionally repressive conformation, where helix 12 is located within the orthosteric ligand-binding pocket instead, and discuss mechanistic implications.

    • Jinsai Shang
    • , Sarah A. Mosure
    •  & Douglas J. Kojetin
  • Article
    | Open Access

    The β1-adrenergic receptor (β1AR) is a G-protein-coupled receptor (GPCRs) that binds catecholamine ligands. Here the authors employ site-specific labelling and 19F NMR measurements to characterise the structural changes and dynamics in the cytoplasmic region of β1AR upon agonist stimulation and coupling to a Gs-protein-mimetic nanobody.

    • J. Niclas Frei
    • , Richard W. Broadhurst
    •  & Daniel Nietlispach
  • Article
    | Open Access

    Although transcription factor (TF) cooperativity is widespread, a global mechanistic understanding of the role of TF cooperativity is still lacking. Here the authors introduce a statistical learning framework that provides structural insight into TF cooperativity and its functional consequences based on next generation sequencing data and provide mechanistic insights into TF cooperativity and its impact on protein-phenotype interactions.

    • Ignacio L. Ibarra
    • , Nele M. Hollmann
    •  & Judith B. Zaugg
  • Article
    | Open Access

    In retroviruses, the capsid protein (CA) forms a shell surrounding the viral core. Here the authors combine cryo-electron microscopy with NMR and X-ray crystallography to examine the CA structure from the human endogenous retrovirus HML2 (HERV-K) and determine the structures of four Fullerene CA closed shells that reveal the molecular basis of capsid assembly.

    • Oliver Acton
    • , Tim Grant
    •  & Peter B. Rosenthal
  • Article
    | Open Access

    Myeloid-derived growth factor (MYDGF) is an endoplasmic reticulum protein of therapeutic interest because it promotes tissue repair in a murine model of myocardial infarction. Here the authors present the NMR structure of human MYDGF and attribute function to a set of residues conserved in MYDGFs but not the vanin base domain, which has a similar fold.

    • Valeriu Bortnov
    • , Marco Tonelli
    •  & Deane F. Mosher
  • Article
    | Open Access

    Parkinson’s disease (PD) and Multiple System Atrophy (MSA) are characterized by the pathological accumulation of α-synuclein. Here the authors employ fluorescent probes, electron microscopy and NMR spectroscopy to study the properties of α-synuclein aggregates that were amplified from patient brain extracts and observe a greater structural diversity among PD patients compared to MSA patients.

    • Timo Strohäker
    • , Byung Chul Jung
    •  & Markus Zweckstetter
  • Article
    | Open Access

    Polar-faceted nanocrystals often have complex atomic surface configurations that are very difficult to characterize. Here, the authors are able to determine detailed structural information about the polar facets of ceria nanocubes by using 17O and 1H solid-state NMR spectroscopy, in combination with density functional theory calculations.

    • Junchao Chen
    • , Xin-Ping Wu
    •  & Luming Peng
  • Article
    | Open Access

    CKK domain containing CAMSAP/Patronins recognise and regulate microtubule (MT) minus end dynamics. Here the authors compare cryo-EM structures of MT-bound human CKK and Naegleria gruberi CKK which lacks minus-end binding preference, finding NgCKK has a different interaction with, and inability to remodel, its MT binding site, shedding light on the CAMSAP/Patronin end binding mechanism.

    • Joseph Atherton
    • , Yanzhang Luo
    •  & Carolyn A. Moores
  • Article
    | Open Access

    Nuclear spins in diamond have applications in quantum technologies and NMR methods but their performance can be limited by relaxation processes that are difficult to characterise. Ajoy et al. develop a T1 noise spectroscopy method to identify the dominant relaxation channel and propose a mitigation strategy.

    • A. Ajoy
    • , B. Safvati
    •  & A. Pines
  • Article
    | Open Access

    Metal-mediated base pairs expand the repertoire of nucleic acid structures and dynamics. Here, the authors prepared a metallo-DNA duplex including two C-Hg(II)-T base pairs separated by six normal Watson-Crick base pairs and investigated its solution structure and dynamics using NMR spectroscopy.

    • Olivia P. Schmidt
    • , Simon Jurt
    •  & Nathan W. Luedtke
  • Article
    | Open Access

    Developing inhibitors that target specific protein-protein interactions (PPIs) is challenging. Here, the authors show that target selectivity and PPI blocking can be achieved simultaneously with PPI inhibitors that contain two functional modules, and create a paralog-selective PSD-95 inhibitor as proof-of-concept.

    • Charlotte Rimbault
    • , Kashyap Maruthi
    •  & Matthieu Sainlos
  • Article
    | Open Access

    Processing bodies are membrane less organelles that contain enzymes involved in mRNA turnover, among them enhancer of decapping 3 (Edc3). Here the authors use solid- and solution-state NMR spectroscopy to characterize the structural organization and dynamics of Edc3 and find that its interactions with RNA and between the different Edc3 domains are largely preserved in the phase-separated state.

    • Reinier Damman
    • , Stefan Schütz
    •  & Marc Baldus