Featured
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Books & Arts |
DNA dynamos
A look at how life's mechanics are deciphered at the molecular level fascinates Mark Haw.
- Mark Haw
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News & Views |
A toolbox for protein design
Some of the principles underlying how amino-acid sequences determine the three-dimensional structures of proteins have been defined. This has enabled a successful approach to designing protein folds from scratch. See Article p.222
- Birte Höcker
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Letter |
Accelerated disassembly of IgE–receptor complexes by a disruptive macromolecular inhibitor
The interaction between IgE and its receptor FcεRI underlies many allergic responses; here the structure and mechanism of a newly engineered DARPin inhibitor is presented, revealing that it not only blocks the receptor–ligand interaction but also dissociates already-formed complexes.
- Beomkyu Kim
- , Alexander Eggel
- & Theodore S. Jardetzky
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Letter |
Structure of the chemokine receptor CXCR1 in phospholipid bilayers
NMR spectroscopy is used to determine the three-dimensional structure of the full-length human chemokine receptor CXCR1 in phospholipid bilayers under physiological conditions.
- Sang Ho Park
- , Bibhuti B. Das
- & Stanley J. Opella
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Article |
DAXX envelops a histone H3.3–H4 dimer for H3.3-specific recognition
The crystal structures of the histone chaperone DAXX histone-binding domain bound to a histone H3.3–H4 dimer are described; DAXX wraps around the H3.3–H4 dimer and alters its conformation.
- Simon J. Elsässer
- , Hongda Huang
- & Dinshaw J. Patel
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Article |
Visualizing transient low-populated structures of RNA
This study develops an NMR-based approach that can capture previously inaccessible, highly transient, low-populated ‘excited states’ in RNA; the localized rearrangements in base-pairing giving rise to these states are found to affect function by changing the exposure of residues required for a specific biological process.
- Elizabeth A. Dethoff
- , Katja Petzold
- & Hashim M. Al-Hashimi
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News |
Bacteria replicate close to the physical limit of efficiency
Bacteria reproduce themselves rapidly — but could we make them faster still?
- Philip Ball
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Research Highlights |
How cells maintain chains
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Letter |
Structural insights into electron transfer in caa3-type cytochrome oxidase
The caa3-type cytochrome oxidase structure described here provides insight into the coupling of energy transduction to the complete reduction of oxygen.
- Joseph A. Lyons
- , David Aragão
- & Martin Caffrey
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Article |
Biophysical mechanism of T-cell receptor triggering in a reconstituted system
After introducing the T-cell receptor and other essential signalling genes, a non-immune cell is capable of displaying the early events of T-cell activation when placed in contact with antigen-presenting cells, and the initial signalling in this reconstituted system is shown to require the spatial reorganization of molecules at the cell interface.
- John R. James
- & Ronald D. Vale
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Letter |
The complex of tmRNA–SmpB and EF-G on translocating ribosomes
Stalled bacterial ribosomes can be rescued by interaction with SmpB protein and a highly structured transfer-messenger RNA, and a cryo-electron microscopy map of this complex now shows how EF-G-dependent translocation of this non-canonical ligand is facilitated by conformational changes in the ribosome and the transfer-messenger RNA.
- David J. F. Ramrath
- , Hiroshi Yamamoto
- & Christian M. T. Spahn
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Article |
Multiple dynamic representations in the motor cortex during sensorimotor learning
Genetically encoded neural activity markers were used in mice to simultaneously follow large populations of motor cortex neurons during sensorimotor learning, revealing that spatially intermingled neurons represent either sensory or motor behaviour, with population-level representations of subsets of motor programs strengthening as training progressed.
- D. Huber
- , D. A. Gutnisky
- & K. Svoboda
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Letter |
Stereospecific binding of a disordered peptide segment mediates BK channel inactivation
Two-step BK channel inactivation mediated by an intrinsically disordered BK β-subunit peptide involves a stereospecific binding interaction that precedes blockade.
- Vivian Gonzalez-Perez
- , Xu-Hui Zeng
- & Christopher J. Lingle
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Letter |
Restoration of grasp following paralysis through brain-controlled stimulation of muscles
A functional electrical stimulation system in primates that is controlled by recordings made from microelectrodes permanently implanted in the brain can be used to control the intensity of stimulation of muscles that are temporarily paralysed by pharmacological motor nerve blockade, thereby restoring voluntary control of the affected muscles; this is a major advance towards similar restoration of hand function in human patients with spinal cord injury.
- C. Ethier
- , E. R. Oby
- & L. E. Miller
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Letter |
Adaptation at the output of the chemotaxis signalling pathway
The motor driving cells during chemotaxis is very sensitive to levels of CheY-P, a signalling protein; counter-intuitively, the motor is tuned to the cells’ output of CheY-P by adjusting the number of CheY-P receptors in the motor, thereby increasing or decreasing the motor’s sensitivity to CheY-P.
- Junhua Yuan
- , Richard W. Branch
- & Howard C. Berg
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Research Highlights |
Claustrophobic DNA in tug of war
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News |
Souped-up cyclotrons offer isotope remedy
Approach could avert shortage of valuable tracers for medical imaging.
- Nicola Jones
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Review Article |
Functional complexity and regulation through RNA dynamics
- Elizabeth A. Dethoff
- , Jeetender Chugh
- & Hashim M. Al-Hashimi
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Letter |
Structure of the carboxy-terminal region of a KCNH channel
The function of the KCNH family of potassium channels is critical for the repolarization of the cardiac action potential and the regulation of neuronal excitability; here, the X-ray crystal structure of the cyclic-nuclotide-binding homology domain of the zebrafish ELK channel is reported.
- Tinatin I. Brelidze
- , Anne E. Carlson
- & William N. Zagotta
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Article |
X-ray structures of LeuT in substrate-free outward-open and apo inward-open states
The X-ray crystal structure of LeuT, the bacterial homologue of the neurotransmitter sodium symporter family, is reported in the outward-open and inward-open states.
- Harini Krishnamurthy
- & Eric Gouaux
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Letter |
Tail-assisted pitch control in lizards, robots and dinosaurs
Comparison of real lizards with a robotic version and a dinosaur model shows that lizards use their tails to control body pitch in aerial motion by means of transfer of angular momentum from the body to the tail.
- Thomas Libby
- , Talia Y. Moore
- & Robert J. Full
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Letter |
Recovery rates reflect distance to a tipping point in a living system
Decreased rates of recovery from perturbations, or critical slowing down, are demonstrated in a living system, indicating that recovery rates can be used to probe the resilience of complex systems.
- Annelies J. Veraart
- , Elisabeth J. Faassen
- & Marten Scheffer
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Article |
Antiparallel EmrE exports drugs by exchanging between asymmetric structures
NMR and single molecule FRET experiments show that antiparallel EmrE dimers interconvert between two identical but oppositely oriented conformations that are each open only to one side of the membrane.
- Emma A. Morrison
- , Gregory T. DeKoster
- & Katherine A. Henzler-Wildman
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Letter |
Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+ channel
The crystal structure of the calcium-bound gating ring of a calcium- and voltage-activated potassium channel shows in detail how the effect of calcium binding on the gating ring produces the conformational change from closed to open.
- Peng Yuan
- , Manuel D. Leonetti
- & Roderick MacKinnon
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Letter |
Structure of full-length Drosophila cryptochrome
- Brian D. Zoltowski
- , Anand T. Vaidya
- & Brian R. Crane
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Letter |
Electrically driven directional motion of a four-wheeled molecule on a metal surface
- Tibor Kudernac
- , Nopporn Ruangsupapichat
- & Ben L. Feringa
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Letter |
Atomic-resolution dynamics on the surface of amyloid-β protofibrils probed by solution NMR
- Nicolas L. Fawzi
- , Jinfa Ying
- & G. Marius Clore
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News & Views |
More than a bystander
The tendency of hydrophobic surfaces to aggregate in water is often invoked to explain how biomolecules recognize and bind to each other. Water seems to have a much more active role in these processes than had been thought.
- Philip Ball
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Letter |
Structural basis for a [4Fe-3S] cluster in the oxygen-tolerant membrane-bound [NiFe]-hydrogenase
- Yasuhito Shomura
- , Ki-Seok Yoon
- & Yoshiki Higuchi
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Letter |
Self-replication of information-bearing nanoscale patterns
- Tong Wang
- , Ruojie Sha
- & Nadrian C. Seeman
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Letter |
Conformational changes in the G protein Gs induced by the β2 adrenergic receptor
- Ka Young Chung
- , Søren G. F. Rasmussen
- & Roger K. Sunahara
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Letter |
Structural basis of RNA recognition and activation by innate immune receptor RIG-I
- Fuguo Jiang
- , Anand Ramanathan
- & Joseph Marcotrigiano
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Research Highlights |
DNA is as elastic as nylon
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Letter |
Structures of the RNA-guided surveillance complex from a bacterial immune system
- Blake Wiedenheft
- , Gabriel C. Lander
- & Eva Nogales
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Letter |
ATP-induced helicase slippage reveals highly coordinated subunits
- Bo Sun
- , Daniel S. Johnson
- & Michelle D. Wang
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Letter |
Mechanical strain in actin networks regulates FilGAP and integrin binding to filamin A
- A. J. Ehrlicher
- , F. Nakamura
- & T. P. Stossel
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Letter |
Solution structure of a minor and transiently formed state of a T4 lysozyme mutant
- Guillaume Bouvignies
- , Pramodh Vallurupalli
- & Lewis E. Kay
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Review Article |
Dynamic molecular processes mediate cellular mechanotransduction
- Brenton D. Hoffman
- , Carsten Grashoff
- & Martin A. Schwartz
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Letter |
Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF
- Cameron D. Mackereth
- , Tobias Madl
- & Michael Sattler
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Article |
Structure and mechanism of the hexameric MecA–ClpC molecular machine
Regulated proteolysis by ATP-dependent proteases have a crucial role in protein quality control in cells. The Clp/Hsp100 proteins of the AAA+ superfamily of ATP-dependent chaperones unfold and translocate proteins into the proteolytic chamber of protease complexes. ClpC requires the adaptor protein MecA for activation and substrate targetting to the ClpCP protease complex. Here, a structural and biochemical analysis is presented of the MecA–ClpC complex revealing organizational principles and providing mechanistic insights into this complex molecular machine.
- Feng Wang
- , Ziqing Mei
- & Yigong Shi
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Article |
Structural basis for the subunit assembly of the anaphase-promoting complex
The APC/C is a large multiprotein complex that functions as an E3 ubiquitin ligase to regulate the cell cycle. Here, the entire APC/C complex is reconstituted, and in combination with structural studies a pseudo-atomic model for 70% of the complex is provided. These results contribute towards a molecular understanding of the roles of individual subunits in APC/C assembly and their interactions with co-activators, substrates and regulatory proteins.
- Anne Schreiber
- , Florian Stengel
- & David Barford
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Letter |
Structural basis for site-specific ribose methylation by box C/D RNA protein complexes
A complex of RNA and protein known as the box C/D RNP catalyses the site-specific modification of RNAs with a 2′-O-methylation group. The structure of the full complex has now been solved, including the guide RNA and either of two substrate RNAs. This structure reveals how the guide and target RNAs are aligned, and how the methyltransferase subunit, fibrillarin, facilitates placement of the target ribose into the active site.
- Jinzhong Lin
- , Shaomei Lai
- & Keqiong Ye
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Article |
Nascent transcript sequencing visualizes transcription at nucleotide resolution
A novel technique called native elongating transcript sequencing (NET-seq) is described, which can quantify transcription with single nucleotide resolution. It is based on sequencing nascent transcripts associated with RNA polymerase II that are captured directly from live cells, and is used to gain insights into polymerase pausing and backtracking and the directionality of transcription.
- L. Stirling Churchman
- & Jonathan S. Weissman
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Letter |
Structure and function of an irreversible agonist-β2 adrenoceptor complex
The X-ray crystal structure of the human β2 adrenergic receptor, a G-protein-coupled receptor (GPCR), covalently bound to a small-molecule agonist is solved. Comparison of this structure with structures of this GPCR in an inactive state and in an antibody-stabilized active state reveals how binding events at both the extracellular and intracellular surfaces stabilize the active conformation of the receptor. Molecular dynamics simulations suggest that the agonist-bound active state spontaneously relaxes to an inactive-like state in the absence of a G protein.
- Daniel M. Rosenbaum
- , Cheng Zhang
- & Brian K. Kobilka
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Letter |
Sensing the anomeric effect in a solvent-free environment
The anomeric effect is a chemical phenomenon that refers to an observed stabilization of six-membered carbohydrate rings when they contain an electronegative substituent at the C1 position of the ring. This stereoelectronic effect influences the three-dimensional shapes of many biological molecules, but the underlying physical origin is unclear. Here it is shown that complexes formed between a truncated peptide motif and an isolated sugar in the gas phase are nearly identical structurally; however, the strength of the polarization of their interactions with the peptide differs greatly. It will be important to re-evaluate the influence, and biological effects, of substituents at position C2 of the six-membered carbohydrate rings.
- Emilio J. Cocinero
- , Pierre Carcabal
- & Benjamin G. Davis
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Letter |
The mechanism of sodium and substrate release from the binding pocket of vSGLT
Here, a comprehensive study of the sodium/galactose transporter (vSGLT) is presented, consisting of molecular dynamics simulations, biochemical characterization and a new crystal structure of the 'inward-open' conformation. These experiments show that sodium exit causes a reorientation of transmembrane helix 1, opening an inner gate required for substrate exit, while also triggering minor rigid-body movements in two sets of transmembrane helical bundles. This cascade of conformational changes is responsible for the proper timing of ion and substrate release.
- Akira Watanabe
- , Seungho Choe
- & Jeff Abramson
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Letter |
Head swivel on the ribosome facilitates translocation by means of intra-subunit tRNA hybrid sites
During translation, tRNAs enter the ribosome and then move sequentially through three sites, known as A, P and E, as they transfer their attached amino acids onto the growing peptide chain. How the ribosome facilitates tRNA translocation between the sites remains largely unknown. Now a study uses multiparticle cryoelectron microscopy of a ribosome bound to the translation elongation factor, EF-G, to get information about tRNA movement. It identifies two new substates and sees that translocation is linked to unratcheting of the 30S ribosomal subunit.
- Andreas H. Ratje
- , Justus Loerke
- & Christian M. T. Spahn
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Letter |
Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography
The E1 and E2 glycoproteins of alphaviruses form heterodimers and assemble into spikes on the virus surface, which mediate receptor binding and endocytosis. When the virion encounters acidic pH in the endosome E1 and E2 dissociate and E1 triggers fusion with the endosomal membrane. Two papers now provide the first crystal structures for glycoprotein complexes incorporating E2 at acidic and neutral pH, respectively. Together they provide insight into how fusion activation is controlled in alphaviruses.
- James E. Voss
- , Marie-Christine Vaney
- & Félix A. Rey
Ubiquitin chain conformation regulates recognition and activity of interacting proteins
Crystal structure of nucleotide-free dynamin