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| Open AccessLigand efficacy modulates conformational dynamics of the µ-opioid receptor
Studies on the µ-opioid receptor using fluorescent labelling of intracellular residues and energy transfer experiments in the presence of different ligands with or without G-protein binding reveals conformational changes that correlate to ligand efficacy.
- Jiawei Zhao
- , Matthias Elgeti
- & Chunlai Chen
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The structure and physical properties of a packaged bacteriophage particle
Multiresolution computational simulations generate all-atom models of a complete packaged virus particle.
- Kush Coshic
- , Christopher Maffeo
- & Aleksei Aksimentiev
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Article
| Open AccessInfluence of pump laser fluence on ultrafast myoglobin structural dynamics
Ultrafast time-resolved serial femtosecond crystallography is used to investigate a photodissociation reaction in a protein, revealing the strong impact of the pump laser fluence on the structural changes and the reaction mechanism.
- Thomas R. M. Barends
- , Alexander Gorel
- & Ilme Schlichting
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Article
| Open AccessStructures of a sperm-specific solute carrier gated by voltage and cAMP
This study proposes a molecular mechanism of voltage activation in SLC9C1, a transporter essential for male fertility.
- Valeria Kalienkova
- , Martin F. Peter
- & Cristina Paulino
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Article |
A pentameric TRPV3 channel with a dilated pore
High-speed atomic force microscopy single-molecule imaging and cryo-EM analysis discover and reveal the structure of a TRPV3 pentamer, providing evidence for a non-canonical pentameric TRP-channel assembly, laying the foundation for new directions in TRP channel research.
- Shifra Lansky
- , John Michael Betancourt
- & Simon Scheuring
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Article
| Open AccessMega-scale experimental analysis of protein folding stability in biology and design
Large-scale assays using cDNA display proteolysis are used to measure the folding stabilities of protein domains, providing a method to quantify the effects of mutations on protein folding, with applications in protein design.
- Kotaro Tsuboyama
- , Justas Dauparas
- & Gabriel J. Rocklin
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Article |
RNA conformational propensities determine cellular activity
Systematic alteration of HIV-1 TAR RNA and quantitative determination of its propensity to bind to the Tat protein establish a key role role for a rare and short-lived RNA state in Tat-dependent transactivation in cells.
- Megan L. Ken
- , Rohit Roy
- & Hashim M. Al-Hashimi
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Article
| Open AccessVisualizing the disordered nuclear transport machinery in situ
Previously shown as a 60-nm hole in the nuclear pore complex, the transport machinery by FG-nucleoporins is mapped.
- Miao Yu
- , Maziar Heidari
- & Edward A. Lemke
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Article
| Open AccessCFTR function, pathology and pharmacology at single-molecule resolution
A structure–function analysis of cystic fibrosis transmembrane conductance regulator shows its two nucleotide-binding domains dimerize before channel opening, and reveals a mechanism through which conformational changes in the channel regulate chloride conductance.
- Jesper Levring
- , Daniel S. Terry
- & Jue Chen
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Structural basis of odorant recognition by a human odorant receptor
Through the use of cryo-electron microscopy and molecular dynamics stimulations, mechanistic insight into the binding of an odorant to the human odorant receptor OR51E2 is provided.
- Christian B. Billesbølle
- , Claire A. de March
- & Aashish Manglik
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Structural insights into the mechanism of the sodium/iodide symporter
Mutations in the sodium/iodide symporter (NIS) cause congenital hypothyroidism, and our results yield insights into how NIS selects, couples and translocates anions, thereby establishing a framework for understanding NIS function.
- Silvia Ravera
- , Juan Pablo Nicola
- & Nancy Carrasco
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Article
| Open AccessNonlinear mechanics of human mitotic chromosomes
A method that uses a combination of optical trapping, fluorescence microscopy and microfluidics to analyse the internal structure of chromosomes shows that there is a distinct nonlinear stiffening of the chromosome in response to tension.
- Anna E. C. Meijering
- , Kata Sarlós
- & Gijs J. L. Wuite
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Article |
Time-resolved structural analysis of an RNA-cleaving DNA catalyst
Using high-resolution NMR characterization, the kinetics and dynamics of the catalytic function of a DNAzyme are shown.
- Jan Borggräfe
- , Julian Victor
- & Manuel Etzkorn
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Article |
Structural architecture of the human NALCN channelosome
The structure of the human NALCN channelosome and a model of the gating mechanism are determined.
- Marc Kschonsak
- , Han Chow Chua
- & Jian Payandeh
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Article |
Systems-level effects of allosteric perturbations to a model molecular switch
Interface mutations in the GTPase switch protein Gsp1 (the yeast homologue of human RAN) allosterically affect the kinetics of the switch cycle, revealing a systems-level mechanism of multi-specificity.
- Tina Perica
- , Christopher J. P. Mathy
- & Tanja Kortemme
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Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV
SCAF1 is solely required for supercomplex CIII2CIV assembly and is not involved in the formation of the respirasome (supercomplex CICIII2CIV)
- Irene Vercellino
- & Leonid A. Sazanov
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Cryo-EM structures of full-length Tetrahymena ribozyme at 3.1 Å resolution
Cryo-electron microscopy has been used to determine the structure of the Tetrahymena ribozyme (a catalytic RNA) at sufficiently high resolution to model side chains and metal ions.
- Zhaoming Su
- , Kaiming Zhang
- & Wah Chiu
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Glutamate transporters have a chloride channel with two hydrophobic gates
Glutamate transporters conduct chloride ions through an aqueous channel with hydrophobic gates that forms during the glutamate transport cycle.
- Ichia Chen
- , Shashank Pant
- & Renae M. Ryan
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Article |
Measuring DNA mechanics on the genome scale
A high-throughput, chromosome-wide analysis of DNA looping reveals its contribution to the organization of chromatin, and provides insight into how nucleosomes are deposited and organised de novo.
- Aakash Basu
- , Dmitriy G. Bobrovnikov
- & Taekjip Ha
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Article |
DNA mismatches reveal conformational penalties in protein–DNA recognition
A high-throughput assay that introduces mismatched base pairs into the DNA sequence shows that mismatches can increase transcription factor binding affinity by prepaying some of the energetic cost of distorting the DNA.
- Ariel Afek
- , Honglue Shi
- & Raluca Gordân
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Article |
Red blood cell tension protects against severe malaria in the Dantu blood group
The rare blood group Dantu is known to protect against severe malaria, and a mechanism is proposed here: Dantu red blood cells have a high membrane tension that prevents invasion by malaria parasites.
- Silvia N. Kariuki
- , Alejandro Marin-Menendez
- & Julian C. Rayner
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Article |
DNA surface exploration and operator bypassing during target search
Single-molecule fluorescence resonance energy transfer and real-time confocal laser tracking with fluorescence correlation spectroscopy together characterize how individual lac repressor molecules bypass operator sites while exploring the DNA surface at microsecond timescales.
- Emil Marklund
- , Brad van Oosten
- & Sebastian Deindl
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Cryo-EM structure of SWI/SNF complex bound to a nucleosome
The cryo-electron microscopy structure of the yeast SWI/SNF complex bound to a nucleosome substrate provides insights into the chromatin-remodelling function of this family of protein complexes and suggests mechanisms by which the mutated proteins may cause cancer.
- Yan Han
- , Alexis A Reyes
- & Yuan He
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DNA-loop extruding condensin complexes can traverse one another
Single-molecule visualization shows that condensin—a motor protein that extrudes DNA in one direction only—can encounter and pass a second condensin molecule to form a new type of DNA loop that gathers DNA from both sides.
- Eugene Kim
- , Jacob Kerssemakers
- & Cees Dekker
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HP1 reshapes nucleosome core to promote phase separation of heterochromatin
The S. pombe HP1 protein Swi6 couples chromatin compaction to phase separation by dynamically exposing buried histone residues within nucleosomes.
- S. Sanulli
- , M. J. Trnka
- & G. J. Narlikar
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Force-induced conformational changes in PIEZO1
Cryo-electron microscopy and high-speed atomic force microscopy reveal that PIEZO1 can reversibly deform its shape towards a planar structure, which may explain how the PIEZO1 channel is gated in response to mechanical stimulation.
- Yi-Chih Lin
- , Yusong R. Guo
- & Simon Scheuring
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Letter |
Rotation tracking of genome-processing enzymes using DNA origami rotors
ORBIT (origami-rotor-based imaging and tracking) is used to track the DNA rotation that results from DNA unwinding by RecBCD helicase and transcription by RNAP at a single-molecule scale and millisecond time resolution.
- Pallav Kosuri
- , Benjamin D. Altheimer
- & Xiaowei Zhuang
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Letter |
A distinct abundant group of microbial rhodopsins discovered using functional metagenomics
An analysis based on functional metagenomics reveals a previously unknown group of microbial light-sensory rhodopsins that are widespread among a diverse range of microorganisms.
- Alina Pushkarev
- , Keiichi Inoue
- & Oded Béjà
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Review Article |
Long-distance navigation and magnetoreception in migratory animals
A Review of the cues and mechanisms used by animals to navigate over long distances, with a particular emphasis on magnetoreception.
- Henrik Mouritsen
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Letter |
Dynamic allostery can drive cold adaptation in enzymes
By engineering entropy-tuning changes into distal sites of a bacterial adenylate kinase, an allosteric tuning mechanism based on protein dynamics is revealed.
- Harry G. Saavedra
- , James O. Wrabl
- & Vincent J. Hilser
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Letter |
Structural principles of distinct assemblies of the human α4β2 nicotinic receptor
Cryo-electron microscopy structures of two stoichiometries of heteromeric acetylcholine receptors in complex with nicotine reveal principles of subunit assembly and the structural basis of the distinctive biophysical and pharmacological properties of the different stoichiometries.
- Richard M. Walsh Jr
- , Soung-Hun Roh
- & Ryan E. Hibbs
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Letter |
Molecular mechanism of GPCR-mediated arrestin activation
Molecular dynamics simulations and site-directed fluorescence spectroscopy show that the transmembrane core and cytoplasmic tail of G-protein-coupled receptors independently and cooperatively activate arrestin.
- Naomi R. Latorraca
- , Jason K. Wang
- & Ron O. Dror
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Letter |
Architecture of an HIV-1 reverse transcriptase initiation complex
A cryo-EM structure of an initiation complex of HIV-1 reverse transcriptase sheds light on the initiation of reverse transcription of viral RNA.
- Kevin P. Larsen
- , Yamuna Kalyani Mathiharan
- & Elisabetta Viani Puglisi
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Letter |
The cryo-electron microscopy structure of human transcription factor IIH
The cryo-electron microscopy structure of the ten-subunit human transcription factor IIH, revealing the molecular architecture of the TFIIH core complex, the detailed structures of its constituent XPB and XPD ATPases, and how the core and kinase subcomplexes of TFIIH are connected.
- Basil J. Greber
- , Thi Hoang Duong Nguyen
- & Eva Nogales
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Analysis |
Ribosomes are optimized for autocatalytic production
The large number of small, similarly sized proteins and the small number of heavy RNA molecules that make up a ribosome reduce the time required for reproduction.
- Shlomi Reuveni
- , Måns Ehrenberg
- & Johan Paulsson
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Article |
Single-molecule analysis of ligand efficacy in β2AR–G-protein activation
Single-molecule FRET imaging provides insights into the allosteric link between the ligand-binding and G-protein nucleotide-binding pockets of the β2 adrenergic receptor (β2AR) and improved understanding of the G-protein activation mechanism.
- G. Glenn Gregorio
- , Matthieu Masureel
- & Scott C. Blanchard
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Article |
Force interacts with macromolecular structure in activation of TGF-β
Integrin αVβ6 binds the transforming growth factor-β1 precursor (pro-TGF-β1) in an orientation that is biologically relevant for force-dependent release of TGF-β from its latent form.
- Xianchi Dong
- , Bo Zhao
- & Timothy A. Springer
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Letter |
Basis of catalytic assembly of the mitotic checkpoint complex
The near-complete in vitro reconstitution of the mitotic spindle assembly checkpoint reveals how the assembly of its effector, the mitotic checkpoint complex, is catalysed.
- Alex C. Faesen
- , Maria Thanasoula
- & Andrea Musacchio
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Letter |
Structural basis of co-translational quality control by ArfA and RF2 bound to ribosome
The structure of the bacterial ribosome in complex with the ArfA and the release factor RF2 shows how ArfA recruits RF2 to terminate translation of messenger RNAs that lack a stop codon in the ribosome.
- Fuxing Zeng
- , Yanbo Chen
- & Hong Jin
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Article |
Structure of the T4 baseplate and its function in triggering sheath contraction
A tour-de-force of structural biology solves the structure of the macromolecular injection machinery used to deliver a phage genome into a bacterium.
- Nicholas M. I. Taylor
- , Nikolai S. Prokhorov
- & Petr G. Leiman
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Article |
Near-atomic resolution visualization of human transcription promoter opening
Cryo-electron microscopy structural models of the human pre-initiation complex at all major steps of transcription initiation at near atomic-level resolution are presented, providing new mechanistic insights into the processes of promoter melting and transcription-bubble formation, as well as an almost complete proposed structural model of all of the pre-initiation complex components and their interactions with DNA.
- Yuan He
- , Chunli Yan
- & Eva Nogales
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Article |
Transcription initiation complex structures elucidate DNA opening
The cryo-electron microscopy structures of yeast initiation complexes containing the transcription factors TBP, TFIIA, TFIIB, TFIIE, and TFIIF and containing either closed or open promoter DNA are reported, providing mechanistic insights into DNA opening and template-strand loading.
- C. Plaschka
- , M. Hantsche
- & P. Cramer
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Article |
Visualizing transient Watson–Crick-like mispairs in DNA and RNA duplexes
dG•dT and rG•rU ‘wobble’ mispairs in DNA and RNA transiently form base pairs with Watson–Crick geometry via tautomerization and ionization with probabilities that correlate with misincorporation probabilities during replication and translation.
- Isaac J. Kimsey
- , Katja Petzold
- & Hashim M. Al-Hashimi
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Letter |
Historical contingency and its biophysical basis in glucocorticoid receptor evolution
By characterizing a very large number of might-have-been evolutionary trajectories starting from a resurrected ancestral protein, the authors show that the evolution of an essential modern protein was contingent on extremely unlikely historical mutations.
- Michael J. Harms
- & Joseph W. Thornton
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Letter |
A Ctf4 trimer couples the CMG helicase to DNA polymerase α in the eukaryotic replisome
This study shows how the yeast Ctf4 protein couples the DNA helicase, Cdc45–MCM–GINS, to DNA polymerase α — the GINS subunit of the helicase and the polymerase use a similar interaction to bind Ctf4, suggesting that, as Ctf4 is a trimer, two polymerases could be simultaneously coupled to a single helicase during lagging-strand synthesis.
- Aline C. Simon
- , Jin C. Zhou
- & Luca Pellegrini
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Letter |
Signal amplification and transduction in phytochrome photosensors
The solution and crystal structures of a bacterial phytochrome photosensory core in both its resting and activated states are determined; switching between closed (resting) and open (activated) forms is found to be mediated by a conserved ‘tongue’, and the structures indicate that smaller changes in the vicinity of the chromophore are amplified in scale as they are transmitted through the tongue and beyond.
- Heikki Takala
- , Alexander Björling
- & Sebastian Westenhoff
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Letter |
Co-crystal structure of a T-box riboswitch stem I domain in complex with its cognate tRNA
The co-crystal structure of the T-box tRNA-binding region, stem I, bound to tRNA is solved, showing that this region not only binds the anticodon, but also cradles the entire tRNA, forming an extended interface; the two T-loop motifs of stem I mediate interactions similar to those of RNase P and the large ribosomal subunit, even though the three species do not share a common evolutionary ancestor.
- Jinwei Zhang
- & Adrian R. Ferré-D’Amaré
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Letter |
Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids
A human lipid transfer protein (GLTPD1, named here CPTP) is shown to regulate eicosanoid production by mediating the intermembrane transfer of the phosphorylated sphingolipid ceramide-1-phosphate through a non-vesicular transport mechanism elucidated by structural, functional and biological data.
- Dhirendra K. Simanshu
- , Ravi Kanth Kamlekar
- & Dinshaw J. Patel
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Letter |
DNA unwinding heterogeneity by RecBCD results from static molecules able to equilibrate
The bacterial RecBCD helicase/nuclease shows broad, and apparently static, heterogeneity in the unwinding rate manifest by individual molecules: here it is shown that transiently halting an enzyme during processive translocation allows for a change, most likely conformational, such that the velocity of the molecule after pausing can fall anywhere within the spectrum of rates seen for a population.
- Bian Liu
- , Ronald J. Baskin
- & Stephen C. Kowalczykowski