Molecular biophysics articles within Nature Communications

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  • Article
    | Open Access

    Mevalonate diphosphate decarboxylase (MDD) is a key enzyme in the mevalonate pathway and catalyses the decarboxylation of mevalonate-5-diphosphate to isopentenyl diphosphate. Here, the authors provide insights into the conformational changes that occur during substrate binding of MDD and the subsequent enzymatic reaction steps by determining the substrate and intermediate bound crystal structures of Enterococcus faecalis MDD.

    • Chun-Liang Chen
    • , Lake N. Paul
    •  & Cynthia V. Stauffacher

  • 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

    Menthol in mints elicits a coolness sensation by selective activation of TRPM8 ion channel. Here authors dock menthol to TRPM8 and systematically validate their menthol binding models with thermodynamic mutant cycle analysis in functional tests, and shed light on TRPM8 activation by menthol at the atomic level.

    • Lizhen Xu
    • , Yalan Han
    •  & Fan Yang

  • Article
    | Open Access

    Microtubules are dynamic tubulin polymers which elongate by addition of bent guanosine triphosphate tubulin to the tips of curving protofilaments. Here authors use Brownian dynamics modeling and electron cryotomography to show that the lateral activation energy barrier in tubulin-tubulin interactions is a key parameter for this process, controlling the development of high pulling forces.

    • Nikita B. Gudimchuk
    • , Evgeni V. Ulyanov
    •  & J. Richard McIntosh

  • Article
    | Open Access

    Zika xrRNAs survive in host cells because they can be unwound and copied by replicases, but resist degradation by exonucleases. Here authors use atomistic models and simulations and uncover that pulling into a pore the xrRNA \({3}^{\prime}\) end, as done by replicases, causes progressive unfolding; pulling the \({5}^{\prime}\) end, as done by exonucleases, triggers molecular tightening.

    • Antonio Suma
    • , Lucia Coronel
    •  & Cristian Micheletti

  • Article
    | Open Access

    Computer-aided design of protein-ligand binding is important for the development of novel drugs. Here authors present an approach to use the recently re-parametrized coarse-grained Martini model to perform unbiased millisecond sampling of protein-ligand binding interactions of small drug-like molecules.

    • Paulo C. T. Souza
    • , Sebastian Thallmair
    •  & Siewert J. Marrink

  • Article
    | Open Access

    Archaeal type IV pili (T4P) mediate adhesion to surfaces and are receptors for hyperthermophilic archaeal viruses. Here, the authors present the cryo-EM structures of two archaeal T4P from Pyrobaculum arsenaticum and Saccharolobus solfataricus and discuss evolutionary relationships between bacterial T4P, archaeal T4P and archaeal flagellar filaments.

    • Fengbin Wang
    • , Diana P. Baquero
    •  & Edward H. Egelman

  • Article
    | Open Access

    An increasing number of amyloid structures are determined. Here, the authors present the structure-based amyloid core sequence prediction method Cordax that is based on machine learning and allows the detection of aggregation-prone regions with higher solubility, disorder and surface exposure, and furthermore predicts the structural topology, orientation and overall architecture of the resulting putative fibril core.

    • Nikolaos Louros
    • , Gabriele Orlando
    •  & Joost Schymkowitz

  • Article
    | Open Access

    While infrared nanospectroscopy methods based on thermomechanical detection (AFM-IR) enables the acquisition of absorption spectra at the nanoscale, single molecule detection has not been possible so far. Here, the authors present off-resonance, low power and short pulse infrared nanospectroscopy (ORS-nanoIR), which allows measuring infrared absorption spectra at the single molecule level in a time scale of seconds with high throughput and demonstrate that the secondary structure of single protein molecules can be determined with this method.

    • Francesco Simone Ruggeri
    • , Benedetta Mannini
    •  & Tuomas P. J. Knowles

  • Article
    | Open Access

    Multi-subunit Cullin (CUL)-RING ligases (CRL) form the largest family of E3 ligases and are composed of a substrate receptor, a CUL, and a RING-box (RBX) protein. Here, the authors use cryo-EM and HDX-MS to characterise the ASB9 CUL-RING E3 ligase and present the structure of ASB9-ELOB/C bound to the substrate creatine kinase and the full-length CUL5 structure in complex with RBX2, and they propose a revised allosteric mechanism for CUL-E3 ligase function.

    • Ryan J. Lumpkin
    • , Richard W. Baker
    •  & Elizabeth A. Komives

  • Article
    | Open Access

    Small molecule polyamines participate in diverse aspects of cell growth and differentiation and are known to regulate ion channel gating. Here authors reveal that cellular polyamines control nicotinic acetylcholine receptor (nAChR) biogenesis, and either catabolic degradation or inhibition of polyamine production augments nAChR assembly.

    • Madhurima Dhara
    • , Jose A. Matta
    •  & David S. Bredt

  • Article
    | Open Access

    F1Fo ATP synthase consists of two coupled rotary molecular motors: the soluble ATPase F1 and the transmembrane Fo. Here, the authors present cryo-EM structures of E. coli ATP synthase in four discrete rotational sub-states at 3.1-3.4 Å resolution and observe a rotary sub-step of the Fo motor cring that reveals the mechanism of elastic coupling between the two rotary motors, which is essential for effective ATP synthesis.

    • Meghna Sobti
    • , James L. Walshe
    •  & Alastair G. Stewart

  • Article
    | Open Access

    The mechanism of PARP1-dependent poly-ADP-ribosylation in response to DNA damage is still under debate. Here, the authors use ATR-FTIR spectroscopy to provide time-resolved insights into the molecular details of this process under near physiological conditions.

    • Annika Krüger
    • , Alexander Bürkle
    •  & Aswin Mangerich

  • Article
    | Open Access

    T4 Lysozyme (T4L) is a model protein whose structure is extensively studied. Here the authors combine single-molecule and ensemble FRET measurements, FRET-positioning and screening and EPR spectroscopy to study the structural dynamics of T4L and describe its conformational landscape during the catalytic cycle by an extended Michaelis–Menten mechanism and identify an excited conformational state of the enzyme.

    • Hugo Sanabria
    • , Dmitro Rodnin
    •  & Claus A. M. Seidel

  • 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

    Core-fucosylation of the N-glycan core is an essential biological modification and the α1,6- fucosyltransferase FUT8 is the only enzyme in humans that catalyses this modification through the addition of an α-1,6-linked fucose to N-glycans. Here the authors provide insights into FUT8 substrate recognition by determining the 1.95 Å crystal structure of human FUT8 complexed with GDP and a biantennary complex N-glycan.

    • Ana García-García
    • , Laura Ceballos-Laita
    •  & Ramon Hurtado-Guerrero

  • Article
    | Open Access

    In voltage-gated potassium (KV) channels, the voltage-sensing domain (VSD) undergoes activation states to trigger pore opening via electro–mechanical (E–M) coupling. Here authors show that KV7.1 undergoes a two-stage E–M coupling mechanism during voltage-dependent activation.

    • Panpan Hou
    • , Po Wei Kang
    •  & Jianmin Cui

  • Article
    | Open Access

    To carry out their function, transcription factors must efficiently recognize specific DNA sequence targets, a complex problem in the context of eukaryotic chromatin. Here the authors use single-molecule biophysical experiments, statistical mechanical theory and bioinformatics analyses to conclude that interactions with non-target sequences near promoters serve to increase overall affinity and targeting efficiency.

    • Milagros Castellanos
    • , Nivin Mothi
    •  & Victor Muñoz

  • Article
    | Open Access

    Native mass spectrometry allows monitoring the folding and interactions of multiple coexisting species but its temporal resolution is traditionally limited. Here, the authors develop a temperature-jump electrospray source for mass spectrometry that enables fast kinetics experiments at different temperatures.

    • Adrien Marchand
    • , Martin F. Czar
    •  & Renato Zenobi

  • Article
    | Open Access

    The important tuberculosis drug pyrazinamide (PZA) is converted to its active form pyrazinoic acid (POA) in Mycobacterium tuberculosis (Mtb). Here the authors identify the pantothenate biosynthesis pathway enzyme aspartate decarboxylase (PanD) as the target of PZA and determine the POA bound Mtb PanD crystal structure.

    • Qingan Sun
    • , Xiaojun Li
    •  & James C. Sacchettini

  • Article
    | Open Access

    Annexins are cytoplasmic proteins, which bind to membranes exposing negatively charged phospholipids in a Ca2+-dependent manner. Here the authors use high-speed atomic force microscopy and other techniques to show that annexin-V self-assembles into highly structured lattices that lead to a membrane phase transition on PS-rich membranes.

    • Yi-Chih Lin
    • , Christophe Chipot
    •  & Simon Scheuring

  • Article
    | Open Access

    Many RNA systems possess highly ordered 3-D structures that are essential to their function. Here the authors demonstrate that the long non-coding RNA Braveheart possesses a flexible but defined 3-D structure which is remodeled upon binding the protein CNBP.

    • Doo Nam Kim
    • , Bernhard C. Thiel
    •  & Karissa Y. Sanbonmatsu

  • Article
    | Open Access

    The contraction of cardiac and skeletal muscles is regulated by Ca2+ released from the sarcoplasmic reticulum in muscle cells. Here the authors provide molecular insights into Ca2+ regulation of muscle contraction by determining the cryo-EM structures of the human cardiac muscle thin filament in the absence and presence of Ca2+.

    • Yurika Yamada
    • , Keiichi Namba
    •  & Takashi Fujii

  • Article
    | Open Access

    Torsional stress is generated during DNA replication and transcription, however, the propagation of twist in condensed chromatin is poorly understood. Here the authors measure how force and torque impact chromatin fibers and find that the fibers fold into a left-handed superhelix that can be stabilized by positive torsion, suggesting that chromatin fibers stabilize nucleosomes under torsional stress.

    • Artur Kaczmarczyk
    • , He Meng
    •  & Nynke H. Dekker

  • Article
    | Open Access

    The poly(ADP-ribose) polymerases play a key role in maintaining genomic integrity by detecting DNA damage and mediating repair. Here the authors characterize the kinetics of PARP1 binding to a variety of nucleosomes harbouring DNA double-strand breaks.

    • Deepti Sharma
    • , Louis De Falco
    •  & Curt A. Davey

  • Article
    | Open Access

    The bacterial flagellar hook is a molecular universal joint that connects the rotary motor and long helical propeller of the bacterial flagellum. Here the authors present the 3.6 Å resolution cryo-EM structure of the native supercoiled Salmonella hook that provides insights into the dynamic changes of subunit conformations and intermolecular interactions of the hook protein FlgE.

    • Takayuki Kato
    • , Fumiaki Makino
    •  & Keiichi Namba

  • Article
    | Open Access

    Programmed ribosomal frameshifting (PRF) is an alternative translation strategy that causes controlled slippage of the ribosome along the mRNA, changing the sequence of the synthesized protein. Here the authors provide a thermodynamic framework that explains how mRNA sequence determines the efficiency of frameshifting.

    • Lars V. Bock
    • , Neva Caliskan
    •  & Helmut Grubmüller

  • Article
    | Open Access

    Riboswitches bind intracellular metabolites and control bacterial gene expression. Here, by using X-ray crystallography, molecular dynamics simulations, and single-molecule fluorescence resonance energy transfer, the authors show how a local Mn2+ ion-binding signal is transduced across the yybP-ykoY riboswitch from Xanthomonas oryzae.

    • Krishna C. Suddala
    • , Ian R. Price
    •  & Nils G. Walter

  • Article
    | Open Access

    Microtubules (MTs) are well-studied cytoskeleton components, but have primarily been investigated using fixation or invasive techniques. Here, the authors use label-free second harmonic (SH) fluorescence and correlative light electron microscopy to pinpoint determinants required for SH from MTs.

    • V. Van Steenbergen
    • , W. Boesmans
    •  & P. Vanden Berghe

  • Article
    | Open Access

    RNA chaperones, such as the hepatitic C virus (HCV) core protein, are proteins that aid in the folding of nucleic acids. Here authors use single‐molecule spectroscopy and simulation to show that the HCV core protein acts as a flexible macromolecular counterion which facilitates nucleic acid folding.

    • Erik D. Holmstrom
    • , Zhaowei Liu
    •  & Benjamin Schuler

  • Article
    | Open Access

    The heat-sensitive ion channel TRPV1 is essential to temperature sensing in mammals and other animals. Here the authors find that the platypus form of TRPV1 does not desensitize, identify the mechanism underlying this property, and show that knock-in of this form of the receptor in mice leads to deficits in heat sensitivity.

    • Lei Luo
    • , Yunfei Wang
    •  & Ren Lai

  • Article
    | Open Access

    Analysis of side-chain motions by NMR has so far been restricted to small proteins and methyl-bearing side chains. Here, the authors present NMR methods based on 13C direct detection of highly deuterated protein samples that yield sharp and well-resolved signals and allow the characterisation of side-chain conformational dynamics of six different amino acid types in medium-to-large proteins.

    • Ruth B. Pritchard
    •  & D. Flemming Hansen

  • Article
    | Open Access

    The cellular functions of arrestins are determined in part by the pattern of phosphorylation on the G protein-coupled receptors (GPCRs) to which arrestins bind. Here, authors use a library of synthetic phosphopeptide analogues of the GPCR rhodopsin C-terminus and determine the ability of these peptides to bind and activate arrestins using a variety of biochemical and biophysical methods.

    • Daniel Mayer
    • , Fred F. Damberger
    •  & Dmitry B. Veprintsev

  • Article
    | Open Access

    Phagocytosis of pathogens is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface. Here authors show that myosin 1e and myosin 1f link the actin cytoskeleton to the membrane and are required for efficient phagocytosis of antibody-opsonized targets.

    • Sarah R. Barger
    • , Nicholas S. Reilly
    •  & Nils C. Gauthier

  • Article
    | Open Access

    The small heat-shock protein HSP27 occurs predominantly in oligomeric forms, which makes its structural characterisation challenging. Here the authors employ CPMG and high-pressure NMR with native mass spectrometry and biophysical assays to show that the active monomeric form of HSP27 is substantially disordered and highly chaperone-active.

    • T. Reid Alderson
    • , Julien Roche
    •  & Andrew J. Baldwin

  • Article
    | Open Access

    The characterization of biomacromolecule structural vibrations has been impeded by a broad continuous vibrational density of states obscuring molecule specific vibrations. A terahertz microscopy system using polarization control produces signatures to dynamically fingerprint proteins and a RNA G-quadruplex.

    • Katherine A. Niessen
    • , Mengyang Xu
    •  & Andrea G. Markelz

  • Article
    | Open Access

    The biological functions of lipids critically depend on their highly diverse molecular structures. Here, the authors determine the mass-resolved collision cross sections of 456 sphingolipid and glycerophospholipid species, providing a reference for future structural lipidomics studies.

    • Katrina L. Leaptrot
    • , Jody C. May
    •  & John A. McLean

  • Article
    | Open Access

    Somatic mutations within antibody framework regions (FWR) can alter structural flexibility, but their role in maturation of broadly neutralizing antibodies (bnAbs) is unclear. Here the authors show how FWR mutations impact interdomain conformational flexibility and paratope plasticity during bnAb development.

    • Rory Henderson
    • , Brian E. Watts
    •  & S. Munir Alam

  • Article
    | Open Access

    Mammalian transcription factors (TFs) differ broadly in their DNA binding properties. Here authors quantify mitotic chromosome binding (MCB) of 501 TFs and suggest that MCB can be used as a proxy for non-specific TF-DNA interactions that regulate TF search for specific genomic sites.

    • Mahé Raccaud
    • , Elias T. Friman
    •  & David M. Suter

  • Article
    | Open Access

    IRSp53 is a key regulator of filopodia formation and cell migration. Here, the authors elucidate a mechanism of phosphorylation-dependent inhibition of IRSp53 by 14-3-3, which impedes the interactions of IRSp53 with membranes and downstream cytoskeletal effectors.

    • David J. Kast
    •  & Roberto Dominguez

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