Molecular biophysics articles within Nature Communications

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  • Article
    | Open Access

    Omecamtiv Mecarbil (OM) is a small molecule allosteric effector of cardiac myosin in clinical trials for treatment of systolic heart failure. Here the authors determine the crystal structure of an OM-bound human β-cardiac myosin motor domain to provide molecular level insight into the mechanism of drug action.

    • Donald A. Winkelmann
    • , Eva Forgacs
    •  & Ann M. Stock
  • Article
    | Open Access

    The ryanodine receptor (RyR) is a large multi-domain ion channel that functions to release calcium from the endoplasmic or sarcoplasmic reticulum. Here the authors present crystal structures of the SPRY1 and tandem repeat domains of RyR, allowing precise positioning of the domains and linking disease mutations to RyR function.

    • Zhiguang Yuchi
    • , Siobhan M. Wong King Yuen
    •  & Filip Van Petegem
  • Article
    | Open Access

    MATE transporters confer bacterial multidrug resistance by transporting drugs across cell membranes. Here, the authors present new structures of the DinF and NorM MATE transporters and reveal insights into the mechanisms of substrate transport and MATE inhibition by small-molecule pharmaceuticals.

    • Martha Radchenko
    • , Jindrich Symersky
    •  & Min Lu
  • Article
    | Open Access

    Single molecule methods for measuring load dependence are fundamental for molecular motor research. Here, Sung et al. introduce harmonic force spectroscopy, a method that randomly applies varying loads at high frequency, allowing the determination of load dependent parameters of human β-cardiac myosin at physiological ATP concentration.

    • Jongmin Sung
    • , Suman Nag
    •  & James A. Spudich
  • Article
    | Open Access

    G protein-coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins in humans and exhibit diverse activation mechanisms. Here, the authors combine electron microscopy, hydrogen deuterium exchange and Molecular dynamics simulations to gain insight into the activation mechanism of the glucagon receptor.

    • Linlin Yang
    • , Dehua Yang
    •  & Hualiang Jiang
  • Article
    | Open Access

    3D microvessels with complex geometries and intact endothelium can be built in vitro. Using these engineered microvessels, here the authors show that the generation of the pathologic meshwork of the blood protein von Willebrand factor is affected by vessel architecture, flow and the proteolytic activity of ADAMTS13.

    • Ying Zheng
    • , Junmei Chen
    •  & José A. López
  • Article
    | Open Access

    The AIM2 inflammasome complex is essential for defence against a number of human pathogens but how it assembles upon recognition of foreign DNA remains incompletely understood. Here Morrone et al.suggest the AIM2 pyrin domain acts in both DNA binding and filament assembly to generate a structural template for complex assembly.

    • Seamus R. Morrone
    • , Mariusz Matyszewski
    •  & Jungsan Sohn
  • Article
    | Open Access

    In biological systems, large pH-induced conformational changes can be observed in certain proteins, a phenomenon poorly understood at the molecular level. Here the authors describe a peptide with the ability to self-organize into either small or large nanotubes in a pH-dependent manner and detail the mechanism driving the transition.

    • Céline Valéry
    • , Stéphanie Deville-Foillard
    •  & Franck Artzner
  • Article
    | Open Access

    Depletion of calcium from intracellular stores induces interaction between the endoplasmic reticulum STIM1 protein and the plasma membrane ORAI1 channel that facilitates cellular calcium entry. Here Ma et al. characterize a STIM1 gain-of-function mutant and propose a conformational switch that controls ORAI1 gating.

    • Guolin Ma
    • , Ming Wei
    •  & Yubin Zhou
  • Article
    | Open Access

    The cellular function of small GTPases is regulated by switching between active (GTP-bound) and inactive (GDP-bound) states. Here the authors develop nucleotide analogues that can be covalently linked to GTPases via a strategically placed cysteine residue to lock the target GTPase in defined activation states.

    • David Wiegandt
    • , Sophie Vieweg
    •  & Roger S. Goody
  • Article
    | Open Access

    The Hepatitis C virus (HCV) relies on an internal ribosome entry site (IRES) for translation of all the proteins encoded by its single-stranded RNA genome. Here the authors present a near-atomic cryo-EM structure of the HCV IRES bound to the human ribosome, shedding light on the initiation mechanism of HCV's and related IRESs.

    • Nick Quade
    • , Daniel Boehringer
    •  & Nenad Ban
  • Article
    | Open Access

    Mucosal sialoglycans contribute to host–microbe interactions at mucosal surfaces and impact bacterial colonization of the digestive system. Here the authors identify and characterize an intramolecular trans-sialidase produced by the gut bacterium R. gnavusATCC 29149 that may contribute to adaptation to the mucosal environment.

    • Louise E. Tailford
    • , C. David Owen
    •  & Nathalie Juge
  • Article
    | Open Access

    Cellobiose dehydrogenases (CDHs) cooperate with lytic polysaccharide monooxygenases (LPMOs) to catalyse cellulose degradation. Here Tan et al. define the electron transfer pathway in CDH, providing a structural analysis of CDH conformers and of the interaction between CDH and LPMO during cellulose depolymerisation.

    • Tien-Chye Tan
    • , Daniel Kracher
    •  & Christina Divne
  • Article
    | Open Access

    Single molecule spectroscopy can visualise dynamic changes in protein conformation on the submillisecond timescale. Here, Otosu et al. apply two-dimensional fluorescence lifetime correlation spectroscopy to visualise dynamics between seven conformers of cytochrome con the microsecond timescale.

    • Takuhiro Otosu
    • , Kunihiko Ishii
    •  & Tahei Tahara
  • Article
    | Open Access

    During transcription, replication and repair, DNA-binding proteins must find specific interaction sites hidden within a vast excess of genomic DNA. Here the authors use single-molecule tracking to quantitatively determine the contributions of the different processes that underlie target search in human cells.

    • Davide Normanno
    • , Lydia Boudarène
    •  & Maxime Dahan
  • Article
    | Open Access

    Tailed bacteriophages translocate the genome into and out of the capsid through a portal protein assembly located between the phage s head and tail. Here Sun et al. provide a cryo-EM structure of the bacteriophage T4 portal protein assembly, suggesting the functions and evolution of the portal structure.

    • Lei Sun
    • , Xinzheng Zhang
    •  & Michael G. Rossmann
  • Article |

    Allostery, communication between distant parts of a protein, is a key element of enzyme catalysis. Here the authors combine existing experimental data with molecular dynamics simulations and Markov state models to provide insight into the mechanism of ligand-induced allostery within the cyclicnucleotide-binding domain of protein kinase A.

    • Robert D. Malmstrom
    • , Alexandr P. Kornev
    •  & Rommie E. Amaro
  • Article
    | Open Access

    Adenylate kinase (AdK) plays a key role in cellular energy homeostasis by catalysing the reversible magnesium-dependent formation of ADP from AMP and ATP. Here the authors present a detailed analysis of adenylate kinase’s conformational dynamics and characterize a high-energy state of AdK indispensable for catalysis.

    • Michael Kovermann
    • , Jörgen Ådén
    •  & Magnus Wolf-Watz
  • Article
    | Open Access

    The proteasome is a highly regulated complex fundamental for cell homeostasis and a target for cancer therapy. Here the authors use cryo-EM and single-particle analysis to obtain a detailed map of the interactions between each active sites of the core 20S proteasome and the irreversible inhibitor AdaAhx3L3VS.

    • Paula C.A. da Fonseca
    •  & Edward P. Morris
  • Article
    | Open Access

    Sirtuins are NAD+-dependent deacylases implicated in the regulation of stress responses, bioenergetics and epigenetic control. Here the authors describe the crystal structure of a sirtuin-activating compounds (STAC)-sirtuin complex and begin to elucidate the mechanism of sirtuins activation by STACs.

    • Han Dai
    • , April W. Case
    •  & James L. Ellis
  • Article
    | Open Access

    The regulation of iron levels is an important physiological process as excess cellular iron is highly toxic. Here the authors present several structures of a bacterial ferric uptake regulator (Fur) in complex with the Fe2+transport protein operator and Fur box, shedding light on how iron promotes DNA recognition by Fur.

    • Zengqin Deng
    • , Qing Wang
    •  & Zhongzhou Chen
  • Article
    | Open Access

    Nuclear pore complexes (NPCs) are large macromolecular assemblies that mediate the exchange of molecules between the nucleus and cytoplasm. Here the authors present a ∼20 Å cryo-EM structure of the X. laevisNPC in different states of transport to propose a model for the architecture of the NPC’s molecular gate within its central channel.

    • Matthias Eibauer
    • , Mauro Pellanda
    •  & Ohad Medalia
  • Article
    | Open Access

    The investigation of the chemical reactivity of metal centres in metalloproteins in aqueous solution is challenging. Here, the authors demonstrate the use of single molecule force spectroscopy to study the chemical reactivity of the iron-sulfur centre in rubredoxin in aqueous solution.

    • Peng Zheng
    • , Guilherme M. Arantes
    •  & Hongbin Li
  • Article
    | Open Access

    Variations in cell shape must be accommodated by the cell membrane, but how the membrane adjusts to changes in area and volume is not known. Here the authors show that the membrane responds in a nearly instantaneous, purely physical manner involving the flattening or generation of membrane invaginations.

    • Anita Joanna Kosmalska
    • , Laura Casares
    •  & Pere Roca-Cusachs
  • Article
    | Open Access

    EF-G enhances the rate of tRNA–mRNA translocation on the ribosome. Here the authors use single-molecule FRET to follow tRNA translocation in real time, identifying new chimeric intermediates and suggesting how EF-G binding and GTP hydrolysis change the energetic landscape of translocation to accelerate forward tRNA movement.

    • Sarah Adio
    • , Tamara Senyushkina
    •  & Marina V. Rodnina
  • Article |

    While active and inactive conformations of proteins have been characterised, pathways connecting these states remain largely obscure. Pontiggia et al.find that the inactive state of NtrC represents an ensemble of different conformers that interconvert to the active state via multiple pathways.

    • F. Pontiggia
    • , D.V. Pachov
    •  & D. Kern
  • Article
    | Open Access

    Type III restriction–modification enzymes consists of two methylation and one or two restriction subunits. Here the authors report the structure of the full EcoP15I complex bound to DNA, which suggests mechanisms for ATP hydrolysis dependent diffusion along DNA and how a dimeric methyltransferase modifies only one DNA strand.

    • Yogesh K. Gupta
    • , Siu-Hong Chan
    •  & Aneel K. Aggarwal
  • Article |

    Photolyase is an enzyme responsible for repairing DNA which is damaged after exposure to UV light. Here, the authors use site directed mutagenesis and femtosecond spectroscopy to study how photolyase achieves its maximal repair efficiency.

    • Chuang Tan
    • , Zheyun Liu
    •  & Dongping Zhong
  • Article
    | Open Access

    The fundamental processes of protein insertion and translocation at the outer membrane are mediated by Omp85 proteins. Here the authors report structures of the translocase FhaC, showing that the critical L6 loop adopts a conformation similar to that of related insertases; establishing a common structural basis for Omp85 function.

    • Timm Maier
    • , Bernard Clantin
    •  & Vincent Villeret
  • Article
    | Open Access

    TFIIIC is a RNA polymerase III-specific general transcription factor complex essential for tRNA synthesis. Here the authors combine chemical crosslinking/mass spectrometry and X-ray crystallography to define the architecture of TFIIIC and suggest a model for the assembly of pre-initiation complexes at tRNA genes.

    • Gary Male
    • , Alexander von Appen
    •  & Christoph W. Müller
  • Article
    | Open Access

    Whereas epidermal growth factor-induced dimerization is considered essential for EGFR signalling, the structurally related insulin receptor is a disulfide-linked dimer. Here the authors show that C. elegansEGFR is constitutively dimeric and undergoes subtle structural changes upon ligand binding that likely underlie allosteric activation.

    • Daniel M. Freed
    • , Diego Alvarado
    •  & Mark A. Lemmon
  • Article
    | Open Access

    The signal recognition particle plays a key role in the co-translational protein targeting of membrane and secretory proteins. Here the authors report a crystal structure of the ternary SRP complex in signal sequence bound and unbound forms, providing insight into how signal sequence binding is coupled to SRP receptor interaction.

    • Tobias Hainzl
    •  & A. Elisabeth Sauer-Eriksson
  • Article
    | Open Access

    Fibronectin fibres are an important component of the extracellular matrix, supporting cell adhesion, growth and migration. Here the authors combine site-specific protein labelling with single-molecule localization microscopy to provide detailed insights into the molecular organization of native fibronectin fibrils.

    • Susanna Maria Früh
    • , Ingmar Schoen
    •  & Viola Vogel
  • Article
    | Open Access

    Translation of mRNA into proteins is the least accurate process during genetic information transfer. Here the authors suggest—based on 11 high-resolution ribosome crystal structures—that the origin of protein missense errors involves molecular mimicry via tautomerism or ionization.

    • Alexey Rozov
    • , Natalia Demeshkina
    •  & Gulnara Yusupova
  • Article
    | Open Access

    TALEs are programmable DNA-binding proteins with practical use in genome engineering and synthetic biology. Here the authors use single-molecule fluorescence microscopy to establish that TALE proteins function using two distinct DNA-interaction modes during sequence-specific target search.

    • Luke Cuculis
    • , Zhanar Abil
    •  & Charles M. Schroeder
  • Article |

    miRNAs are incorporated into ribonucleoprotein complexes called RNA-induced silencing complexes (RISCs) to exert RNA interference. Here the authors show that translation initiation factor eIF1A interacts with the RISCs component Ago2 to promote miR-451 biogenesis and RNA interference.

    • Tingfang Yi
    • , Haribabu Arthanari
    •  & Gerhard Wagner
  • Article
    | Open Access

    Retinal-bound opsins are widely used tools for optical control of neuronal activity in vivo, so called optogenetics. Here, using molecular simulations, biochemistry, electrophysiology and X-ray crystallography, the authors present new molecular design principles for the generation of blue-shifted variants of microbial rhodopsins.

    • Hideaki E. Kato
    • , Motoshi Kamiya
    •  & Osamu Nureki
  • Article
    | Open Access

    The determination of RNA structures within high-molecular weight protein-RNA complexes in non-crystalline state is technically challenging. Here, the authors describe a solid-state NMR protocol for the determination of RNA structures at high resolution.

    • Alexander Marchanka
    • , Bernd Simon
    •  & Teresa Carlomagno