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Article
| Open AccessQuantitative maps of protein phosphorylation sites across 14 different rat organs and tissues
The function of proteins is often regulated by their phosphorylation at specific amino-acid residues. The authors of this article have catalogued phosphoproteins and their phosphorylation sites in 14 rat organs and tissues, and provide these data as a resource for researchers.
- Alicia Lundby
- , Anna Secher
- & Jesper V. Olsen
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Prediction of variable translation rate effects on cotranslational protein folding
Proteins can undergo folding while being translated by the ribosome, and the extent of this folding is influenced by the rate at which amino acids are added to the nascent chain. This study provides a framework for predicting domain folding probabilities as a function of the kinetics of amino-acid addition.
- Edward P. O'Brien
- , Michele Vendruscolo
- & Christopher M. Dobson
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Article |
Assembly kinetics determine the architecture of α-actinin crosslinked F-actin networks
Processes that regulate the mechanical and dynamic properties of actin cytoskeleton are important for multiple eukaryotic cell functions. In this study, using reconstituted crosslinked actin networks, organization is found to be determined by the competing kinetics of actin gelation and bundle formation.
- Tobias T. Falzone
- , Martin Lenz
- & Margaret L. Gardel
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Article
| Open AccessSerine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb recognition
Phosphorylation of the carboxy-terminal domain of RNA polymerase II is important for controlling gene transcription. In this study, the transcription elongation factor Tefb is shown to phosphorylate serine-5 and its activity is enhanced when the polymerase is already phosphorylated on serine-7.
- Nadine Czudnochowski
- , Christian A. Bösken
- & Matthias Geyer
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Article
| Open AccessThe cytoplasmic coiled-coil mediates cooperative gating temperature sensitivity in the voltage-gated H+ channel Hv1
In the dimeric voltage-gated H+channel, Hv1/VSOP, the gating of each subunit is coupled, but the molecular basis of dimer formation and intersubunit coupling is unclear. This study shows that channel assembly and cooperative gating are mediated by the cytoplasmic domain.
- Yuichiro Fujiwara
- , Tatsuki Kurokawa
- & Yasushi Okamura
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Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm
Humans and rodents normally store more urine in the bladder when fast asleep than when awake. In this study, the production of the gap junction protein connexin43, a regulator of bladder capacity, is shown to oscillate in mouse urinary bladder muscle in synchrony with the circadian clock.
- Hiromitsu Negoro
- , Akihiro Kanematsu
- & Osamu Ogawa
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Article
| Open AccessThe C-terminal helical bundle of the tetrameric prokaryotic sodium channel accelerates the inactivation rate
Many channels have cytosolic domains which regulate channel function. Irieet al. show that the cytosolic C-terminal region of NavSulP, a prokaryotic voltage-gated sodium channel, forms a four-helix bundle which stabilises the tetrameric channel and accelerates channel inactivation.
- Katsumasa Irie
- , Takushi Shimomura
- & Yoshinori Fujiyoshi
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Article
| Open AccessDistinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons
Sodium channel Nav1.7 is essential for acute human pain but its role in chronic neuropathic pain is unclear. Minett and colleagues show that Nav1.7 expression specifically in sympathetic neurons, rather than sensory neurons, is required for the development of chronic neuropathic pain after injury.
- Michael S. Minett
- , Mohammed A. Nassar
- & John N. Wood
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The structure of the FANCM–MHF complex reveals physical features for functional assembly
Fanconi's anaemia is characterized by an inability to repair DNA damage and is associated with mutations in the Fanconi anaemia nuclear complex, which includes the protein FANCM. This study reports the crystal structures of a fragment of FANCM bound to the histone-fold-containing protein complex, MHF1–MHF2.
- Yuyong Tao
- , Changjiang Jin
- & Maikun Teng
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Nanodomain Ca2+ of Ca2+ channels detected by a tethered genetically encoded Ca2+ sensor
Calcium nanodomains arise from the cytoplasmic mouth of calcium channels but have not been directly visualized. In this study, the nanodomain of the CaV2.2 calcium channel is imaged using total internal reflection fluorescence microscopy and a genetically encoded calcium sensor attached to the carboxy terminus.
- Lai Hock Tay
- , Ivy E. Dick
- & David T. Yue
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Article |
Casein kinase 2 reverses tail-independent inactivation of kinesin-1
Kinesin-1 is a motor protein that transports cargo along microtubules and defects in this process can result in neurodegeneration. In this study, a role for casein kinase 2 in regulating the activity of Kinesin-1 is reported, suggesting that signalling molecules can modulate this transport process.
- Jing Xu
- , Babu J. N. Reddy
- & Steven P. Gross
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FAT10 and NUB1L bind to the VWA domain of Rpn10 and Rpn1 to enable proteasome-mediated proteolysis
FAT-10 targets proteins for degradation in a ubiquitin-independent manner and NUB1L accelerates this process. In this study, both FAT-10 and NUB1L are shown to interact with the VWA domain of the Rpn10 subunit of the 26S proteasome, suggesting that this is a receptor site for ubiquitin-like modifiers.
- Neha Rani
- , Annette Aichem
- & Marcus Groettrup
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Article |
Transient activation of specific neurons in mice by selective expression of the capsaicin receptor
The ability to spatially and temporally control excitation of neuronsin vivo is an invaluable tool. By expressing the TRPV1 receptor in specific neuronal populations, Güler et al. have developed a rapid and noninvasive method to stimulate neuronal activity by the simple administration of capsaicin.
- Ali D. Güler
- , Aundrea Rainwater
- & Richard D. Palmiter
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Article
| Open AccessActivation of canonical Wnt signalling is required for TGF-β-mediated fibrosis
Aberrant activation of the TGF-β pathway leads to fibrotic disease. Distler and colleagues show that TGF-β-mediated fibrosis requires the decrease of Dickkopf-1, an antagonist of canonical Wnt signalling, suggesting that the two pathways interact for the manifestation of this disease.
- Alfiya Akhmetshina
- , Katrin Palumbo
- & Jörg H.W. Distler
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Article
| Open AccessStructure of the pentameric ligand-gated ion channel ELIC cocrystallized with its competitive antagonist acetylcholine
The pentameric ligand gated ion channel fromErwinia chrysanthemi(ELIC) is similar in structure to the nicotinic acetylcholine receptor, a member of the Cys-loop receptor family. This study reports the crystal structure of ELIC bound to acetylcholine and shows that acetylcholine is a competitive antagonist of ELIC.
- Jianjun Pan
- , Qiang Chen
- & Pei Tang
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Article |
Dimensional and temporal controls of three-dimensional cell migration by zyxin and binding partners
Molecular and oscillations are common in biology, but periodic cell migrations have not been observed. Fraleyet al. report regular, periodic migrations of cells along tracks generated inside 3D matrices, and show that these 1D oscillations are controlled by zyxin and its binding partners α-actinin and p130Cas.
- Stephanie I. Fraley
- , Yunfeng Feng
- & Denis Wirtz
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Perturbation of sodium channel structure by an inherited Long QT Syndrome mutation
Perturbation of the cardiac voltage-gated sodium channel, NaV1.5, by drugs or inherited mutation can underlie and trigger cardiac arrhythmias. Here, the role of the NaV1.5 carboxy terminus in channel inactivation is investigated, and structural details of an arrhythmia associated H6 mutant are reported.
- Ian W. Glaaser
- , Jeremiah D. Osteen
- & Robert S. Kass
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Article
| Open AccessThe dynamic stator stalk of rotary ATPases
The peripheral stalks of rotary ATPases counteract torque generated by rotation of the central stalk during ATP synthesis or hydrolysis. Stewartet al.report the crystal structure of an A-type ATPase/synthase peripheral stalk and identify bending and twisting motions that permit the radial wobbling of the headgroup.
- Alastair G. Stewart
- , Lawrence K. Lee
- & Daniela Stock
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Article
| Open AccessUnique domain appended to vertebrate tRNA synthetase is essential for vascular development
Seryl-tRNA synthetase is important in vasculogenesis and contains a unique domain at its C-terminus. In this study, the unique domain is shown to target the protein to the nucleus, block expression ofvegfaand be essential for vasculogenesis in zebrafish.
- Xiaoling Xu
- , Yi Shi
- & Xiang-Lei Yang
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Article
| Open AccessThe dynamic relationships between the three events that release individual Na+ ions from the Na+/K+-ATPase
The Na+/K+-ATPase pump exports three Na+ ions for the exchange of two K+ ions, and three transient current components have been associated with Na+ binding and release. Now, these three components are found to be tightly correlated confirming that the binding and release of Na+ions is sequential.
- David C. Gadsby
- , Francisco Bezanilla
- & Miguel Holmgren
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Article
| Open AccessImperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG
Beclin1 is a key regulator of VPS34-related processes, including autophagy. Liet al. solve the crystal structure of Beclin 1 CC domain, an antiparallel dimer that is rendered metastable by a series of a-d' pairings, which determines its ability to form distinct heterodimers either with Atg14L or UVRAG.
- Xiaohua Li
- , Liqiang He
- & Yanxiang Zhao
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Article
| Open AccessActivation of TRPC6 channels is essential for lung ischaemia–reperfusion induced oedema in mice
The signalling cascade involved in lung ischaemia–reperfusion-induced oedema is poorly understood. Using knockout mice, Weissmannet al. propose a model in which reactive oxygen species production by endothelial NOX2 leads to phospholipase C-γ activation, DAG kinase inhibition and subsequent TRPC6 activation.
- Norbert Weissmann
- , Akylbek Sydykov
- & Alexander Dietrich
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Article
| Open AccessThree-dimensional analysis of ribonucleoprotein complexes in influenza A virus
The influenza A virus genome consists of eight RNA segments, which permits genetic reassortment and contributes to the emergence of novel strains with pandemic potential. Here, electron tomography is used to study the three-dimensional structure of ribonucleoprotein complexes within progeny virions.
- Takeshi Noda
- , Yukihiko Sugita
- & Yoshihiro Kawaoka
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Article
| Open AccessELL facilitates RNA polymerase II pause site entry and release
The super elongation complex, which is involved in transcriptional elongation, contains the Eleven-nineteen Lysine-rich Leukemia protein (ELL). In this study, ELL is shown to stabilize RNA polymerase II prior to recruitment into the super elongation complex, suggesting ELL has a role in early transcription elongation.
- Jung S. Byun
- , Temesgen D. Fufa
- & Kevin Gardner
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Article |
Structural rearrangements underlying ligand-gating in Kir channels
Inward rectifier potassium channels are regulated by a range of ligands that act on a common gate, but the structural details of gating are unclear. Here, the molecular motions associated with gating of KirBac1.1 channels are assessed using small molecule fluorescent probes attached to introduced cysteines.
- Shizhen Wang
- , Sun-Joo Lee
- & Colin G. Nichols
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Article
| Open AccessStructure-based mutagenesis reveals the albumin-binding site of the neonatal Fc receptor
Albumin transport proteins circulate in the blood and are protected from degradation by interaction with the neonatal Fc receptor. Andersenet al. investigate the albumin binding site of the neonatal Fc receptor and find pH sensitive ionic networks at the binding interface.
- Jan Terje Andersen
- , Bjørn Dalhus
- & Inger Sandlie
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Article
| Open AccessPKA regulatory subunits mediate synergy among conserved G-protein-coupled receptor cascades
G-protein-coupled receptors sense extracellular cues and transmit the signal to distinct trimeric G-proteins. Stefanet al.show that in response to cAMP, a central and conserved component of the Gαs-coupled receptor cascade, the RII subunit of PKA, specifically binds to and participates in Gαi signaling.
- Eduard Stefan
- , Mohan K. Malleshaiah
- & Stephen W. Michnick
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O-Linked-N-acetylglucosamine on extracellular protein domains mediates epithelial cell–matrix interactions
The modification of proteins with O-linked-N-acetylglucosamine causes regulation of multiple cellular processes. In this study, Sakaidani and colleagues identify an endoplasmic reticulum O-linked-N-acetylglucosamine transferase in Drosophilathat regulates the adhesion of epithelial cells to the extracellular matrix.
- Yuta Sakaidani
- , Tomoko Nomura
- & Tetsuya Okajima
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Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesion
Herpesvirus glycoprotein D binds to nectin 1 and the herpes virus entry mediator protein on the surface of host cells. In this study, Zhanget al. report the crystal structure of glycoprotein D in complex with the immunoglobulin-like domains of nectin 1, which suggests that binding of glycoprotein D to nectin 1 prevents nectin 1 dimerization.
- Na Zhang
- , Jinghua Yan
- & George F Gao
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Article |
Specific inhibition of bacterial RNase T2 by helix 41 of 16S ribosomal RNA
The 30S ribosomal subunit ofEscherichia coliinhibits the RNA-degrading enzyme Ribonuclease T2. Using mutational studies and hybrid ribosomes, Kitahara and Miyazaki show that helix 41 of the 30S ribosomal subunit blocks the enzyme activity, suggesting that helix 41 is required for preventing RNase T2 toxicity.
- Kei Kitahara
- & Kentaro Miyazaki
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Article |
P-Rex1 is required for efficient melanoblast migration and melanoma metastasis
The processes that regulate melanoblast migration during development are also thought to be involved in melanoma metastasis. Here, Prex1 null mice are shown to have a melanoblast migration defect and, when crossed to a mouse model of melanoma, are resistant to metastasis, suggesting a role for Prex1 in metastatic melanoma.
- Colin R. Lindsay
- , Samuel Lawn
- & Owen J. Sansom
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Article |
Self-assembly of DNA nanotubes with controllable diameters
DNA nanotubes could be used to transport nano-cargo and incorporated into nano-devices. In this study, rolling circle amplification is used to generate DNA subunits, and their thermodynamic growth results in the formation of nanotubes with a controlled diameter.
- Ofer I. Wilner
- , Ron Orbach
- & Itamar Willner
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MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a
The methylation of DNA and histone H3 lysine 9 in chromatin are positively correlated. This study shows that the DNA methyl transferase Dnmt3a is methylated, and a crystal structure of Dnmt3a bound to the chromodomain protein MPP8 suggests a molecular mechanism.
- Yanqi Chang
- , Lidong Sun
- & Xiaodong Cheng
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Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision
At light levels where both rods and cones are active, their signals converge into shared downstream retinal circuitry. Using HCN1 deficient mice, this study shows that the signals from cone photoreceptors are overwhelmed when rod output is not regulated, suggesting a mechanism for how these systems interact.
- Mathias W. Seeliger
- , Arne Brombas
- & Frank Müller
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Article |
CD91-dependent programming of T-helper cell responses following heat shock protein immunization
Heat shock proteins bind to CD91 on antigen presenting cells, resulting in the presentation of chaperoned peptides to T cells. Here, heat shock protein binding is shown to induce phosphorylation of CD91 and stimulate the production of cytokines, thus priming various T-helper cell responses.
- Sudesh Pawaria
- & Robert J. Binder
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Disrupted erythropoietin signalling promotes obesity and alters hypothalamus proopiomelanocortin production
Erythropoietin circulates in the blood and is essential for erythropoiesis but its role in metabolic homeostasis has not been examined. Tenget al. show that when the erythropoietin receptor is only expressed in erthyroid cells, mice develop obesity and insulin resistance, suggesting that the receptor has a key role in fat mass accumulation.
- Ruifeng Teng
- , Oksana Gavrilova
- & Constance Tom Noguchi
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Article
| Open AccessSelective inhibition of microRNA accessibility by RBM38 is required for p53 activity
MicroRNAs bind to the 3′-untranslated region of genes to regulate expression. In this study, an RNA-binding protein, RMB38, is shown to selectively regulate the access of some microRNAs to their targets, and control the expression of some p53 target genes.
- Nicolas Léveillé
- , Ran Elkon
- & Reuven Agami
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Article |
NMDA receptor activation requires remodelling of intersubunit contacts within ligand-binding heterodimers
In non-NMDA glutamate receptors, intersubunit contacts within agonist binding domains affect functional desensitization. Now, NMDA receptor activation, but not desensitization, is shown to involve rearrangements at the heterodimer interface, suggesting that the intersubunit contacts of NMDA and non-NMDA receptors may have distinct functional roles.
- William F. Borschel
- , Swetha E. Murthy
- & Gabriela K. Popescu
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Article |
The ubiquitin ligase HACE1 regulates Golgi membrane dynamics during the cell cycle
The Golgi membrane is fragmented during mitosis and is subsequently fused following cell division and this process is known to be controlled by ubiquitination. In this study, the ubiquitin ligase HACE1 is shown to be targeted to the Golgi membrane and is required for fusion after the completion of mitosis.
- Danming Tang
- , Yi Xiang
- & Yanzhuang Wang
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Article |
A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death
Radiomitigating compounds could be used to protect against ionizing radiation. In this study, mitochondria-targeted oleic and stearic acid derivatives are shown to inhibit pro-apoptotic oxidative events, prevent cell death, and protect mice against lethal doses of radiation.
- Jeffrey Atkinson
- , Alexandr A. Kapralov
- & Valerian E. Kagan
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Article |
Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells
The role of phosphatidylinositol(4,5)bisphosphate in exocytosis is unclear. This study shows that inhibition of the p110δ isoform of PI3-kinase promotes a transient increase in phosphatidylinositol(4,5)bisphosphate, leading to a potentiation of exocytosis in chromaffin cells.
- Peter J. Wen
- , Shona L. Osborne
- & Frédéric A. Meunier
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Review Article |
Capturing the essence of folding and functions of biomolecules using coarse-grained models
Coarse-grained models can be used to study the folding of biological macromolecules such as DNA, RNA and proteins. In this Review, Hyeon and Thirumalai describe recent advances in the use of these theoretical models to describe dynamic processes in biology.
- Changbong Hyeon
- & D. Thirumalai
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Article |
A chloroplast envelope-bound PHD transcription factor mediates chloroplast signals to the nucleus
Retrograde chloroplast signals are essential in coordinating nuclear gene expression, but the mechanism that relays chloroplast signals to the nucleus remains elusive. In this study, a chloroplast envelope-bound transcription factor PTM is shown to transmit chloroplast signals to the nucleus.
- Xuwu Sun
- , Peiqiang Feng
- & Lixin Zhang
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Article |
Smad6-specific recruitment of Smurf E3 ligases mediates TGF-β1-induced degradation of MyD88 in TLR4 signalling
Transforming growth factor-β blocks the activation of pro-inflammatory cytokines, in part by the degradation of Myd88. This study shows that smad ubiquitin regulator proteins are shown to mediate the destruction of Myd8 and are therefore required for the anti-inflammatory effects of transforming growth factor-β.
- Youn Sook Lee
- , Jin Seok Park
- & Seok Hee Park
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Article
| Open AccessMolecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels
The assembly mechanisms of heteromeric ion channels are poorly understood. Using a range of techniques, Shuartet al.determine the mechanism by which rod photoreceptor cyclic nucleotide-gated channels assume a 3:1 stoichiometry of CNGA1 and CNGB1 subunits.
- Noah G. Shuart
- , Yoni Haitin
- & William N. Zagotta
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Article
| Open AccessA CLASP-modulated cell edge barrier mechanism drives cell-wide cortical microtubule organization in Arabidopsis
How microtubules are organized correctly in plant cells is not well understood. Ambroseet al. use 4D imaging and computer modelling to show that sharp cell edges induce microtubule depolymerization and that the microtubule-associated protein CLASP mitigates this process to modulate array organization.
- Chris Ambrose
- , Jun F. Allard
- & Geoffrey O. Wasteneys
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Article
| Open AccessEditing of human KV1.1 channel mRNAs disrupts binding of the N-terminus tip at the intracellular cavity
RNA editing is important in regulating neuronal excitability, and a specific editing event has been shown to alter the permeation pathway of voltage-gate potassium channels. Gonzalezet al.find that the tip of the channel's inactivation gate makes a direct hydrophobic interaction with the edited position.
- Carlos Gonzalez
- , Angelica Lopez-Rodriguez
- & Miguel Holmgren
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Article |
Structural mechanisms of DIAP1 auto-inhibition and DIAP1-mediated inhibition of drICE
The inhibitor of apoptosis protein DIAP1 exists in an auto-inhibited conformation, but the details of its molecular interactions are poorly understood. Here, crystal structures reveal the auto-inhibition mechanism of DIAP1 and show how the active form of the protein binds to the effector caspase drICE.
- Xiaochun Li
- , Jiawei Wang
- & Yigong Shi
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Article |
Outlines of the pore in open and closed conformations describe the gating mechanism of ASIC1
The pore gating mechanism of the proton-activated sodium channel ASIC1 is poorly understood. Canessaet al.study the shape of the ion pathway in the ASIC1 channel in its open and closed states, and reveal the opening, closing and desensitization mechanisms of the channel.
- Tianbo Li
- , Youshan Yang
- & Cecilia M. Canessa
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