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| 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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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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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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Article
| Open AccessArabidopsis nitrate reductase activity is stimulated by the E3 SUMO ligase AtSIZ1
Posttranslational modification of proteins by small ubiquitin-related modifier is a response to stress signalling in plants. Here, theArabdiposisprotein SIZ1 is shown to cause SUMOylation of nitrate reductases 1 and 2 and to increase their activity, suggesting that SIZ1 controls nitrate uptake via SUMOylation.
- Bong Soo Park
- , Jong Tae Song
- & Hak Soo Seo
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Article |
Crystal structure of the human thioredoxin reductase–thioredoxin complex
Thioredoxin reductase 1 is a flavoprotein that is involved in the regulation of redox homeostasis. Fritz-Wolfet al. report the first crystal structures of thioredoxin reductase 1 in complex with its substrate, thioredoxin, and confirm that the enzyme uses a flexible carboxy-terminal arm for electron transport to its substrates.
- Karin Fritz-Wolf
- , Sebastian Kehr
- & Katja Becker
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Article
| Open AccessCalcium modulates force sensing by the von Willebrand factor A2 domain
von Willebrand factor (VWF) multimers mediate primary adhesion and aggregation of platelets. Jakobiet al. reveal a calcium-binding site in the VWF-A2 domain, and show that calcium binding encourages folding of the protein and has a role in mechanosensing.
- Arjen J. Jakobi
- , Alireza Mashaghi
- & Eric G. Huizinga
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Identification and characterization of a multidomain hyperthermophilic cellulase from an archaeal enrichment
Archaea are microorganisms that use a wide range of carbon and energy sources. Grahamet al. describe an archaeal consortium that can grow at temperatures above 90 °C using crystalline cellulose as a carbon source, with potential applications in enzymatic degradation under extreme conditions.
- Joel E. Graham
- , Melinda E. Clark
- & Frank T. Robb
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Article |
TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin
Nitric oxide can be produced by nitric oxide synthase or by nitrite reduction, but whether the latter occurs inside cells is unknown. Here, the TRPV3 ion channel is shown to induce nitrite-dependent nitric oxide production in keratinocytes, where it has a role in thermosensory behaviour and wound healing.
- Takashi Miyamoto
- , Matt J. Petrus
- & Ardem Patapoutian
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Cyclin B-dependent kinase 1 regulates human TRF1 to modulate the resolution of sister telomeres
TRF1 is a telomere binding protein involved in sister telomere cohesion. In this study, the ability of TRF1 to bind to telomeres in mitosis is inhibited by cyclin-dependent kinase 1-mediated phosphorylation, which may facilitate sister telomere resolution during mitosis.
- Megan McKerlie
- & Xu-Dong Zhu
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Article
| Open AccessRequirement of calcium-activated chloride channels in the activation of mouse vomeronasal neurons
The vomeronasal organ detects pheromones, which are thought to activate TRPC2 channels on the surface of vomeronasal neurons. Using TRPC2 knockout mice, the authors show that urinary pheromones can also activate these neurons via calcium-activated chloride channels, suggesting a TRPC2-independent pathway for sensing pheromones.
- SangSeong Kim
- , Limei Ma
- & C. Ron Yu
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Article
| Open AccessInteraction between prion protein and toxic amyloid β assemblies can be therapeutically targeted at multiple sites
The ability of synthetic amyloid β-protein to bind to prion proteins and alter synaptic plasticity has been previously reported. Here the relevance of this binding is investigated in brains of Alzheimer's disease patients and the interaction is shown to be blocked by antibodies to two distinct regions of prion proteins.
- Darragh B. Freir
- , Andrew J. Nicoll
- & John Collinge
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Article
| Open AccessTRAF6 ubiquitinates TGFβ type I receptor to promote its cleavage and nuclear translocation in cancer
TGFβ can function as both a tumour suppressor and tumour promoter under different cellular contexts. Here, the cleavage product of the TGFβ type I receptor is shown to be generated in a TGFβ-dependent manner, and can induce the expression of genes involved in tumour cell invasion.
- Yabing Mu
- , Reshma Sundar
- & Marene Landström
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Potential for interdependent development of tRNA determinants for aminoacylation and ribosome decoding
Aminoacyl-transfer RNA synthetases are conserved between bacteria and eukaryotes; however, bacterial enzymes cannot acylate eukaryote tRNAs. Now, fusion of a human and bacterial enzyme is shown to overcome the species barrier and confer tRNA specificity during both codon selection and proofreading on the ribosome.
- Cuiping Liu
- , Howard Gamper
- & Ya-Ming Hou
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Article
| Open AccessIntron retention in the Drosophila melanogaster Rieske iron sulphur protein gene generated a new protein
Genomes evolve with time but the molecular mechanisms that underlie this process are poorly understood. Gontijoet al. describe a protein that was generated by the retention of an intron in the Drosophila melanogaster Rieske iron sulphur proteingene and show that the resulting protein is translated.
- Alisson M. Gontijo
- , Veronica Miguela
- & Maria Dominguez
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Article
| Open AccessPredicting sites of ADAR editing in double-stranded RNA
ADAR enzymes edit double-stranded RNA, converting adenosines to inosines, and are essential for neuronal function. Eggingtonet al. quantify edit sites in RNA using a Sanger sequencing protocol and use the resulting data to develop algorithms to predict RNA edit sites.
- Julie M. Eggington
- , Tom Greene
- & Brenda L. Bass
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Article |
The neural circuits and sensory channels mediating harsh touch sensation in Caenorhabditis elegans
The mechanisms by which animals distinguish between harsh and gentle touch are unclear. UsingCaenorhabditis elegansas a model system, the authors identify neural circuits and touch-sensitive ion channels that are required for harsh touch sensation.
- Wei Li
- , Lijun Kang
- & X.Z. Shawn Xu
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Article
| Open AccessStructure and Scm3-mediated assembly of budding yeast centromeric nucleosomes
There is debate about the structural organization of the yeast centromeric nucleosome and the role of the nonhistone protein Scm3 in its assembly. Dechassaet al.find that yeast centromeric nucleosomes organize DNA in a left-handed superhelix, and show that Scm3 is a specific nucleosome assembly factor.
- Mekonnen Lemma Dechassa
- , Katharina Wyns
- & Karolin Luger
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Article
| Open AccessTranscription factor IRF8 directs a silencing programme for TH17 cell differentiation
The molecular mechanisms that regulate TH17 cell diversity are poorly understood. Ouyang et al. show that the transcription factor interferon regulatory factor-8 is required for TH17-cell differentiation and that its absence increases the severity of an experimental model of colitis.
- Xinshou Ouyang
- , Ruihua Zhang
- & Huabao Xiong
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Article
| Open AccessIKKβ regulates essential functions of the vascular endothelium through kinase-dependent and -independent pathways
IKK kinases activate nuclear factor-κB, and the activated form of this transcription factor is found in endothelial cells in diseased tissue. In this study, mice lacking IKKβ in the endothelium are generated, and it is shown that defects in endothelial cell function are both IKK kinase activity dependent and independent.
- Noboru Ashida
- , Sucharita SenBanerjee
- & Anthony Rosenzweig
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Article
| Open AccessAurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis
Mitotic exit is controlled by a cell division checkpoint that prevents premature degradation of cyclin B by the anaphase-promoting complex. Saurinet al. show that Aurora B directly regulates timely establishment of this checkpoint by facilitating activation of Mps1 kinase at unattached kinetochores.
- Adrian T. Saurin
- , Maike S. van der Waal
- & Geert J.P.L. Kops
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Article
| Open AccessPhotosynthetic growth despite a broken Q-cycle
The Q-cycle is thought to be an essential energetic component of the photosynthetic electron-transfer chain. Here, Chlamydomonas mutants with an inactive Q-cycle but normal levels ofb6fcomplexes are shown to display photosynthetic growth, demonstrating the dispensability of the Q-cycle in the oxygenic photosynthetic chain.
- Alizée Malnoë
- , Francis-André Wollman
- & Fabrice Rappaport
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An evolutionarily conserved three-dimensional structure in the vertebrate Irx clusters facilitates enhancer sharing and coregulation
TheIrx genes are arranged in clusters and the reason for this arrangement is unclear. Using a chromatin conformation capture assay, the authors show that Irx genes share enhancer elements, suggesting that the gene cluster is required for coregulation of the Irxgenes.
- Juan J. Tena
- , M. Eva Alonso
- & José Luis Gómez-Skarmeta
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Two splice variants of the IDD14 transcription factor competitively form nonfunctional heterodimers which may regulate starch metabolism
The alternative splicing of genes increases the number and diversity of proteins produced within a cell. Seoet al. demonstrate that the beta form of the alternatively spliced Arabidopsis gene, IDD14, is produced under cold conditions and may have a role in regulating starch accumulation.
- Pil Joon Seo
- , Mi Jung Kim
- & Chung-Mo Park
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Mutual adaptation of a membrane protein and its lipid bilayer during conformational changes
The detailed interactions of membrane proteins with their lipid environment are poorly understood. Sonntaget al. use low-resolution X-ray crystallographic data and molecular dynamics simulations to study the manner in which the sarcoendoplasmic reticulum Ca2+–ATPase adapts to different membrane environments.
- Yonathan Sonntag
- , Maria Musgaard
- & Lea Thøgersen
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α-Mannosidase 2C1 attenuates PTEN function in prostate cancer cells
PTEN is a phosphatase that regulates the phosphatidylinositol-3 kinase signalling pathway and is inactivated in many tumour types. Heet al.show that a mannosidase, α-mannosidase 2C1, can inactivate PTEN in prostate cancer cells, and that PTEN-positive human prostate tumours overexpress α-mannosidase 2C1.
- Lizhi He
- , Catherine Fan
- & Damu Tang
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Article |
Two-dimensional enzyme diffusion in laterally confined DNA monolayers
Little is known about the effects of molecular crowding and confinement on biomolecule function. Castronovoet al. investigate the reactions of restriction enzymes with DNA confined in bushy matrices and find that the enzymes enter at the side of the matrix before diffusing two-dimensionally.
- Matteo Castronovo
- , Agnese Lucesoli
- & Giacinto Scoles
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Article |
Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors
N-methyl-D-aspartate receptors mediate excitatory synaptic transmission, and those containing GluN2D subunits have an unusually long deactivation time. Vance et al. show that the conformational variability of the ligand-binding domain and the structure of the activating ligand influence deactivation time.
- Katie M. Vance
- , Noriko Simorowski
- & Hiro Furukawa
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Article
| Open AccessRespiratory distress and perinatal lethality in Nedd4-2-deficient mice
In vitrostudies have suggested that the ubiquitin ligase, Nedd4-2, regulates several proteins, including the epithelial sodium channel. Here by examining Nedd4-2-deficient mice, the authors demonstrate that Nedd4-2 is essential for epithelial sodium channel regulation, fetal and postnatal lung function and animal survival.
- Natasha A. Boase
- , Grigori Y. Rychkov
- & Sharad Kumar
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LTD is a protein required for sorting light-harvesting chlorophyll-binding proteins to the chloroplast SRP pathway
Chloroplast proteins are synthesized in the cytosol and imported into the chloroplast before being delivered to the thylakoids. The authors report that an ankyrin-repeat protein, LTD, is essential for the routing of chlorophyll-binding proteins to the signal recognition particle pathway.
- Min Ouyang
- , Xiaoyi Li
- & Lixin Zhang
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Article
| Open AccessAnnexin-A5 assembled into two-dimensional arrays promotes cell membrane repair
Eukaryotic cell plasma membranes possess a mechanism to repair tears caused by stimuli such as mechanical stress. The authors demonstrate that annexin-A5, when assembled into two-dimensional arrays in the presence of calcium, is required for membrane repair.
- Anthony Bouter
- , Céline Gounou
- & Alain R. Brisson
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Article |
Adhesive water networks facilitate binding of protein interfaces
The formation of hydrophilic protein–protein interactions cannot be explained by charge–charge interactions. Here, molecular simulations reveal that water forms an adhesive hydrogen-bonded network between proteins, stabilizing intermediate states before the bound complex forms.
- Mazen Ahmad
- , Wei Gu
- & Volkhard Helms
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Article |
The acetylation of tau inhibits its function and promotes pathological tau aggregation
Phosphorylation of the microtubule-associated protein tau is associated with disease, but other post-translational modifications of tau are not well studied. Here, Cohenet al. study the acetylation of tau and suggest that this form of the protein may be associated with tauopathies.
- Todd J. Cohen
- , Jing L. Guo
- & Virginia M. Y. Lee
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Article
| Open AccessLipid-dependent gating of a voltage-gated potassium channel
Lipid phosphodiesters affect the conformation of certain potassium channels, but the details of the lipid-channel interactions are unclear. Here, the KvAP channel is found to switch from an active to a resting state when the channels are transferred from a phospholipid membrane to a bilayer lacking phosphodiesters.
- Hui Zheng
- , Weiran Liu
- & Qiu-Xing Jiang
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Article
| Open AccessErrors in the measurement of voltage-activated ion channels in cell-attached patch-clamp recordings
Voltage-activated ion channels can be measured in neurons using the cell-attached patch-clamp technique. Williams and Wozny show that this technique is prone to errors that are caused by the flow of current through the ion channels; a method to correct for these discrepancies is described.
- Stephen R. Williams
- & Christian Wozny
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Article
| Open AccessThe structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain
CXXC domain proteins bind to CpG DNA sequences and influence chromatin modification. Xuet al.report crystal structures of the CXXC protein CFP1, a component of the SETD1 histone H3K4 methyl transferase complex, and study the molecular mechanisms of DNA-binding specificity.
- Chao Xu
- , Chuanbing Bian
- & Jinrong Min
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Article
| Open AccessStructural basis for the recognition and cleavage of histone H3 by cathepsin L
Cathepsin L mediates proteolysis of the histone H3 tail and is a factor in cell-cycle progression and cellular differentiation. Adams-Cioabaet al. report crystal structures of an inactive mutant of the protease complexed with substrate peptides, and find that it is highly accommodating of modified substrates.
- Melanie A. Adams-Cioaba
- , Joanne C. Krupa
- & Jinrong Min
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Article |
A bacterial proteorhodopsin proton pump in marine eukaryotes
Proteorhodopsin is used by prokaryotes to generate energy from light. In this study, the authors describe a prokaryote-to-eukaryote horizontal gene transfer of a bacterial proteorhodopsin gene to dinoflagellates, suggesting that these eukaryotes can also use proteorhodopsin to obtain light and produce energy.
- Claudio H. Slamovits
- , Noriko Okamoto
- & Patrick J. Keeling
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Article |
Rad23 escapes degradation because it lacks a proteasome initiation region
Rad23 accompanies ubiquitinated substrates to the proteasome for destruction but manages to avoid degradation. In this study, Fishbainet al.show that Rad23 escapes because it lacks an effective initiation region; therefore, the proteasome is unable to engage the protein and unfold it.
- Susan Fishbain
- , Sumit Prakash
- & Andreas Matouschek
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Article
| Open AccessC-terminal UBA domains protect ubiquitin receptors by preventing initiation of protein degradation
Rad23 and Dsk2 bind polyubiquitylated proteins and escort them to the proteasome for destruction. In this study, Heinenet al.investigate the molecular mechanisms that protect the C-terminal UBA domains of Rad23 and Dsk2 from proteasomal destruction.
- Christian Heinen
- , Klàra Ács
- & Nico P. Dantuma
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Article |
ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA
Uridines at the wobble position of transfer RNA anticodons are usually modified to allow efficient decoding of messenger RNA codons. In this study, ALKBH8 is shown to be a bifunctional transfer RNA modification enzyme required for the formation of a novel diastereomeric pair of modified wobble uridines.
- Erwin van den Born
- , Cathrine B. Vågbø
- & Pål Ø. Falnes
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Article |
A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa
The CATSPER heteromeric ion channel complex is required for male fertility and six protein components of the complex have been identified. In this study, the authors identify a seventh gene, CATSPERδ, which is necessary for functional CatSper channels and hyperactivated sperm motility.
- Jean-Ju Chung
- , Betsy Navarro
- & David E. Clapham
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Article
| Open AccessConformational rearrangement of gastric H+,K+-ATPase induced by an acid suppressant
The gastric proton pump, H+,K+-ATPase, contributes to stomach acidification and is a target of acid suppressants. Here, the three-dimensional structure of the pump is determined using electron crystallography, providing the first structural information about the binding of a new class of acid suppressants.
- Kazuhiro Abe
- , Kazutoshi Tani
- & Yoshinori Fujiyoshi
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Article
| Open AccessCrystallographic observation of 'induced fit' in a cryptophane host–guest model system
Cryptophane-A is a prototypical organic host molecule that binds reversibly to neutral guest molecules. Taratulaet al.report X-ray structures of cryptophane-A complexed with a range of host molecules to show that the cryptophane host–guest system exhibits ‘induced fit’.
- Olena Taratula
- , P. Aru Hill
- & Ivan J. Dmochowski
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Article |
The phospholipase D1 pathway modulates macroautophagy
Macroautophagy involves remodelling of intracellular membranes, but the role of lipids and lipid enzymes in this process is poorly understood. Here, the authors demonstrate that phospholipase D1, an enzyme that catalyses the production of phosphatidic acid, has a modulatory role in the autophagy process in mammalian cells.
- Claudia Dall'Armi
- , Andrés Hurtado-Lorenzo
- & Gilbert Di Paolo
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Article
| Open AccessSystems-wide temporal proteomic profiling in glucose-starved Bacillus subtilis
Identifying the transcripts and proteins that fluctuate in response to stimuli provides important information for understanding cell physiology. In this study, 52% of theBacillus subtilispredicted proteome is identified following glucose starvation, revealing further insight into protein dynamics at a global scale.
- Andreas Otto
- , Jörg Bernhardt
- & Dörte Becher
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Article |
High rates of photobiological H2 production by a cyanobacterium under aerobic conditions
Hydrogen production using photosynthetic bacteria is an appealing energy source, but typically the bacteria require anaerobic conditions. Here, the authors report a wild-type cyanobacterium strain that shows very high rates of hydrogen production under aerobic environmental conditions.
- Anindita Bandyopadhyay
- , Jana Stöckel
- & Himadri B. Pakrasi
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Article
| Open AccessStretching fibronectin fibres disrupts binding of bacterial adhesins by physically destroying an epitope
Bacteria express adhesive proteins on their surface that recognize fibronectin. Using a mechanical stretch assay and steered molecular dynamics, Chabriaet al. demonstrate that the binding of a bacterial adhesin to fibronectin is mechanoregulated, suggesting that bacteria can sense tissue fibre stretching.
- Mamta Chabria
- , Samuel Hertig
- & Viola Vogel
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Article
| Open AccessSubstrate docking to γ-secretase allows access of γ-secretase modulators to an allosteric site
γ-Secretase modulators have promise in the treatment of Alzheimer's disease, but their molecular target is uncertain. Here, fluorescence resonance energy transfer is used to determine that the γ-secretase allosteric site is within the γ-secretase complex and that substrate docking is required for modulators to access the site.
- Kengo Uemura
- , Katherine C. Farner
- & Oksana Berezovska
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