Kinetics articles within Nature Communications

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  • Article
    | Open Access

    Here the authors perform modelling to reveal that the timescale of actin-VASP interactions plays a critical role in actin ring formation and filament length determines droplet deformation in VASP droplets: predictions from the model were tested against VASP GAB mutant.

    • Aravind Chandrasekaran
    • , Kristin Graham
    •  & Padmini Rangamani

  • Article
    | Open Access

    Studying RNA decay remains a challenging task. Here, the authors present a technology that enables inducible rapid degradation of targeted mRNAs. Visualizing mRNA decay dynamics unveils insights into P-body function in RNA metabolism.

    • Lauren A. Blake
    • , Leslie Watkins
    •  & Bin Wu

  • Article
    | Open Access

    The authors show G protein subtype selectivity at the β1-adrenergic receptor is driven by the binding kinetics of ternary complex formation. Bound to G protein, the receptor adopts conformations that differ from its agonist-bound solution states.

    • Andrew J. Y. Jones
    • , Thomas H. Harman
    •  & Daniel Nietlispach

  • Article
    | Open Access

    Here the authors combine 19 F NMR and femtosecond transient absorption to characterise the structural origin of the multiphasic quenching dynamics in various species of BLUF domains, highlighting the importance of the heterogeneous active-site H-bond network.

    • Yalin Zhou
    • , Siwei Tang
    •  & Dongping Zhong

  • Article
    | Open Access

    Adhesive type-1 pili from Escherichia coli are filamentous protein complexes consisting of a short tip and a long rod formed by up to several thousand copies of a major subunit. Here, Giese et al. reconstitute the entire type-1 pilus rod assembly reaction in vitro, using all constituent protein subunits, and identify a subunit that acts as an irreversible assembly terminator.

    • Christoph Giese
    • , Chasper Puorger
    •  & Rudi Glockshuber

  • Article
    | Open Access

    Here, the reaction of the suicide inhibitor sulbactam with the M. tuberculosis β-lactamase (BlaC) is investigated with time-resolved crystallography. Singular Value Decomposition is implemented to extract kinetic information despite changes in unit cell parameters during the time-course of the reaction.

    • Tek Narsingh Malla
    • , Kara Zielinski
    •  & Marius Schmidt

  • Article
    | Open Access

    Bicarbonate (HCO3−) is critical in sperm for stimulation of cAMP synthesis during fertilization, though there is dispute over how  HCO3− is transported into sperm. Here the authors use limit-of-detection LC/MS to characterize sperm protein expression and show that HCO3− is produced from CO2 diffusion into sperm rather than active transport.

    • Elena Grahn
    • , Svenja V. Kaufmann
    •  & U.Benjamin Kaupp

  • Article
    | Open Access

    Here the authors use fast kinetics, X-ray crystallography, and cryo-EM to uncover the mechanism of ribosome inhibition by amikacin and kanamycin. They find that amikacin binds near the P-site tRNA, offering new strategies to fight antibiotic resistance.

    • Savannah M. Seely
    • , Narayan P. Parajuli
    •  & Matthieu G. Gagnon

  • Article
    | Open Access

    NMDA receptors are glutamate-gated ion channels that regulate fast signaling in the brain. Here, the authors show that the opening and closing patterns of the channel derive from the action of two gates that are regulated by distinct subunits.

    • Johansen B. Amin
    • , Miaomiao He
    •  & Lonnie P. Wollmuth

  • Article
    | Open Access

    It is known that the T cell co-receptor CD4 greatly enhances the capacity of T cell receptor (TCR) signalling, triggered by the peptide-bound MHC molecule. Here authors show that the mechanistic basis for the enhancement is the co-operative binding of TCR and CD4 to the MHC-peptide complex.

    • Muaz Nik Rushdi
    • , Victor Pan
    •  & Cheng Zhu

  • Article
    | Open Access

    Light-matter interaction can induce changes to the properties of the system by creating hybrid collective states of light and molecular excitations, the so called polaritons. Here the authors use femtosecond pump-probe spectroscopy to explore exciton-polariton dynamics in a photosynthetic protein, light harvesting 2 complexes, and find evidence for rapid energy transfer to dark polariton states.

    • Fan Wu
    • , Daniel Finkelstein-Shapiro
    •  & Tönu Pullerits

  • Article
    | Open Access

    Meprin α is a proteolytic regulator of the extracellular matrix that forms enormous oligomeric filaments of unknown purpose. Here, the authors determine by cryo-EM the structural basis of the meprin supercoiled filament and further characterise a small molecule inhibitor bound to its active site.

    • Charles Bayly-Jones
    • , Christopher J. Lupton
    •  & James C. Whisstock

  • Article
    | Open Access

    Here the authors report the cryo-EM structure of a triple-mutant of the anti-microbial peptide plectasin, PPI42, assembling in a pH- and concentration dependent manner into helical non-amyloid fibrils. The fibrils formation is reversible, and follows a sigmoidal kinetics. The fibrils adopt a right-handed helical superstructure composed by two protofilaments, stabilized by an outer hydrophobic ring and an inner hydrophobic centre. These findings reveal that α/β proteins can natively assemble into fibrils.

    • Christin Pohl
    • , Gregory Effantin
    •  & Pernille Harris

  • Article
    | Open Access

    RecBCD is a remarkably fast DNA helicase. Using a battery of biophysical methods, Zananiri et. al reveal additional, non-catalytic ATP binding sites that increase the ATP flux to the catalytic sites that allows fast unwinding when ATP is scarce.

    • Rani Zananiri
    • , Sivasubramanyan Mangapuram Venkata
    •  & Arnon Henn

  • Article
    | Open Access

    Cas9 off-target sites can be predicted by many bioinformatics tools. Here the authors present low complexity mechanistic model that characterizes SpCas9 kinetics in free-energy terms, allowing quantitative prediction of off-target activity in bulk-biochemistry, single molecule, and whole-genome profiling experiments.

    • Behrouz Eslami-Mossallam
    • , Misha Klein
    •  & Martin Depken

  • Article
    | Open Access

    UVR8 is a plant photoreceptor that dissociates into monomers after sensing UV. Here, via ultrafast spectroscopy and computational calculations, the authors describe the dynamics of charge separation and charge neutralization in UVR8 and describe how these unzip interactions at the dimer interface.

    • Xiankun Li
    • , Zheyun Liu
    •  & Dongping Zhong

  • Article
    | Open Access

    Here the authors use nanovesicles, microfluidics and single-molecule methods to observe individual ligand binding events that stimulate activation of CNG ion channels. They find that binding is followed by a conformational change of either independent or weakly cooperative binding domains.

    • Vishal R. Patel
    • , Arturo M. Salinas
    •  & Marcel P. Goldschen-Ohm

  • Article
    | Open Access

    Molecular chaperones from the Hsp70 family can break up protein aggregates, including amyloids. Here, the authors utilize microfluidic diffusional sizing to assess the mechanism of α-synuclein (αS) disaggregation by the Hsc70–DnaJB1–Apg2 system, and show that single αS molecules are removed directly from the fibril ends.

    • Matthias M. Schneider
    • , Saurabh Gautam
    •  & Tuomas P. J. Knowles

  • Article
    | Open Access

    How chromosomes, which are polymers with nearly billion base pairs, are packaged in the restricted nuclear volume is not well understood. Here, the authors combine polymer physics, nonequilibrium fluctuation theorem, and simulations to quantitatively predict the force-dependent velocity and step-size distribution of condensin, which facilitates the folding of chromosomes by loop extrusion.

    • Ryota Takaki
    • , Atreya Dey
    •  & D. Thirumalai

  • Article
    | Open Access

    m6A RNA post-transcriptional modification changes RNA hybridization kinetics. Here the authors show that the methylamino group can adopt syn-conformation pairing with uridine with a mismatch-like conformation in RNA duplex. They also develop a quantitative model that predicts how m6A affects the kinetics of hybridization.

    • Bei Liu
    • , Honglue Shi
    •  & Hashim M. Al-Hashimi

  • Article
    | Open Access

    Aβ oligomers (AβO) are thought to represent the main toxic species in Alzheimer’s disease but very high Aβ concentrations are required to study them in vitro and it remains unknown what role these off-pathway oligomers play in vivo. Here, the authors use a dimeric variant of Aβ termed dimAβ, where two Aβ40 units are linked, which facilitates to study AβO formation kinetics and they observe that Aβ off-pathway oligomer formation is strongly accelerated at endo-lysosomal pH, while amyloid fibril formation is delayed. Furthermore, the authors demonstrate that dimAβ is a disease-relevant model construct for pathogenic AβO formation by showing that dimAβ AβOs target dendritic spines and induce AD-like somatodendritic Tau missorting.

    • Marie P. Schützmann
    • , Filip Hasecke
    •  & Wolfgang Hoyer

  • Article
    | Open Access

    The nucleation mechanisms of biological protein phase separation are poorly understood. Here, the authors perform time-resolved SAXS experiments with the low-complexity domain (LCD) of hnRNPA1 and uncover multiple kinetic regimes on the micro- to millisecond timescale. Initially, individual proteins collapse. Nucleation then occurs via two steps distinguished by their protein cluster size distributions.

    • Erik W. Martin
    • , Tyler S. Harmon
    •  & Tanja Mittag

  • Article
    | Open Access

    The primary energy conversion step in photosynthesis, charge separation, takes place in the reaction center. Here the authors investigate the heliobacterial reaction center using multispectral two-dimensional electronic spectroscopy, identifying the primary electron acceptor and revealing the charge separation mechanism.

    • Yin Song
    • , Riley Sechrist
    •  & Jennifer P. Ogilvie

  • Article
    | Open Access

    Spy is an ATP independent chaperone that can act as both a holdase and a foldase towards topologically simple substrates. Assessing the interaction of Spy and apoflavodoxin, a complex client, the authors show that Spy’s activity is substrate specific. Spy binds partially unfolded states of apoflavodoxin tightly, which limits the possibility of folding and converts Spy to a pure holdase.

    • Rishav Mitra
    • , Varun V. Gadkari
    •  & James C. A. Bardwell

  • Article
    | Open Access

    The assembly of actin filaments into distinct cytoskeletal structures plays a critical role in cell physiology. Here, the authors use a combination of live cell imaging and in vitro single molecule binding measurements to show that tandem calponin homology domains (CH1–CH2) are sensitive to actin filament conformation, biasing their subcellular localization.

    • Andrew R. Harris
    • , Pamela Jreij
    •  & Daniel A. Fletcher

  • Article
    | Open Access

    The intrinsically disordered linker histone H1.0 and prothymosin α form a complex which exhibits slow exchange between bound and unbound populations at low protein concentrations and fast exchange at high concentrations. Here authors explain this observation by the formation of transient ternary complexes favored at high protein concentrations that accelerate the exchange.

    • Andrea Sottini
    • , Alessandro Borgia
    •  & Benjamin Schuler

  • Article
    | Open Access

    GABAA receptors mediate most inhibitory synaptic transmission in the brain. Here authors used concatemeric α1β2γ2 GABAA receptors to introduce gain-of-desensitization mutations one subunit at a time, revealing non-concerted rearrangements with a key contribution of the γ2 subunit during desensitization.

    • Marc Gielen
    • , Nathalie Barilone
    •  & Pierre-Jean Corringer

  • Article
    | Open Access

    Cyanobacterial photosystem I has a highly conserved core antenna consisting of eleven subunits and more than 90 chlorophylls. Here via CryoEM and spectroscopy, the authors determine the location of a red-shifted low-energy chlorophyll that allows harvesting of longer wavelengths of light.

    • Hila Toporik
    • , Anton Khmelnitskiy
    •  & Yuval Mazor

  • Article
    | Open Access

    Photoreceptor UVR8 in plants senses environmental UV levels through 26 structural tryptophan residues, but the role of 18 of them was unknown. The authors show, by experiments and computations, how these form a light-harvesting network that funnels the excitation to the pyramid centers enhancing the light-perception efficiency.

    • Xiankun Li
    • , Haisheng Ren
    •  & Dongping Zhong

  • Article
    | Open Access

    Rescue of ribosomes stalled on non-stop mRNA is essential for cell viability, and several rescue systems to resolve stalling exist in bacteria. Here, the authors use rapid kinetics and cryo-EM to reveal the pathway and selectivity mechanism of ArfB-mediated ribosome rescue.

    • Kai-Hsin Chan
    • , Valentyn Petrychenko
    •  & Marina V. Rodnina

  • 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 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

    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 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

    Molecular details that underlie mechanical properties of spider silk are of great interest to material scientists. Here, the authors report a previously unknown three-state mechanism of folding and an expanded structure of a spider silk protein that may contribute to elasticity of spider silk.

    • Charlotte Rat
    • , Julia C. Heiby
    •  & Hannes Neuweiler

  • Article
    | Open Access

    How interactions between binding partners form or break is hidden in the transition paths from the encounter to the formation of a stable complex. Here authors use single‐molecule spectroscopy to measure the transition path times for the association of two intrinsically disordered proteins that form a folded dimer upon binding and identify a metastable encounter complex.

    • Flurin Sturzenegger
    • , Franziska Zosel
    •  & Benjamin Schuler

  • Article
    | Open Access

    Metal ions at the active site of an enzyme act as cofactors and their dynamic fluctuations might influence enzyme activity. Here authors use single-molecule FRET to study λ-exonuclease and find that metal-ion-coordination is correlated with enzymatic reaction-steps.

    • Wonseok Hwang
    • , Jungmin Yoo
    •  & Gwangrog Lee

  • Article
    | Open Access

    Hypoxia inducible factor (HIF)-2α transcription factor is mutated in polycythemia and various neuroendocrine tumors. Here the authors present the crystal structure of a HIF-2α peptide bound to the pVHL-elongin B-elongin C (VBC) heterotrimeric complex and propose a classification scheme for HIF-2α mutations that helps to predict disease phenotype outcome.

    • Daniel Tarade
    • , Claire M. Robinson
    •  & Michael Ohh

  • Article
    | Open Access

    How intrinsically disordered proteins (IDPs) undergo a coupled folding and binding reaction with their molecular targets remains to be understood. Here authors use single-molecule FRET to assess the contribution of cis/trans isomerization of peptidyl-prolyl bonds in regulating IDP interactions.

    • Franziska Zosel
    • , Davide Mercadante
    •  & Benjamin Schuler

  • Article
    | Open Access

    Chromatin fibers undergo continuous structural rearrangements but their dynamic architecture is poorly understood. Here, the authors use single-molecule FRET to determine the structural states and interconversion kinetics of chromatin fibers, monitoring their effector protein-dependent dynamic motions.

    • Sinan Kilic
    • , Suren Felekyan
    •  & Beat Fierz

  • Article
    | Open Access

    An understanding of the dynamics of drug binding and unbinding processes is important for drug discovery. Here, the authors give insights into the binding mechanism of small drug-like molecules to human Hsp90 by combining thermodynamics and kinetics studies as well as molecular dynamics simulations.

    • M. Amaral
    • , D. B. Kokh
    •  & M. Frech

  • Article
    | Open Access

    GalNAc transferases’ (GalNAc-Ts) catalytic domains are connected to a lectin domain through a flexible linker. Here the authors present a structural analysis of GalNAc-T4 that implicates the linker region as modulator of the orientations of the lectin domain, which in turn imparts substrate specificity.

    • Matilde de las Rivas
    • , Erandi Lira-Navarrete
    •  & Ramon Hurtado-Guerrero

  • Article
    | Open Access

    Myosin VI (MVI) is known to interact with RNA Polymerase II and to play non-cytoplasmic roles in cells. Here, the authors provide evidence that the transcription co-activator NDP52 regulates MVI binding to DNA and that MVI interacts with nuclear receptors to drive gene expression.

    • Natalia Fili
    • , Yukti Hari-Gupta
    •  & Christopher P. Toseland

  • Article
    | Open Access

    KCNQ1 is a voltage-gated potassium channel that is important in cardiac and epithelial function. Here the authors present a mechanism for KCNQ1 activation and inactivation in which voltage sensor activation promotes pore opening more effectively in the intermediate open state than the fully open state, generating inactivation.

    • Panpan Hou
    • , Jodene Eldstrom
    •  & Jianmin Cui

  • Article
    | Open Access

    The cytoplasm’s crowdedness leads one to expect that cell water is different from bulk water. By measuring the rotational motion of water molecules in living cells, Tros et al. find that apart from a small fraction of water solvating biomolecules, cell water has the same dynamics as bulk water.

    • Martijn Tros
    • , Linli Zheng
    •  & Sander Woutersen

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