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Keywords: mTOR
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Essays Biochem (2022) EBC20220079.
Published: 30 November 2022
... and stimulates the release of autophagolysosomes in microglial cells . J. Immunol. 182 , 2051 – 2062 19201858 10.4049/jimmunol.0802577 139. Kim J.E. , Ko A.R. , Hyun H.W. , Min S.J. and Kang T.C. ( 2018 ) P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated...
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Potential roles of astrocytic P2X 7 R in synaptic function and protein clea...
Published: 30 November 2022
Figure 1 Potential roles of astrocytic P2X 7 R in synaptic function and protein clearance in AD In AD brain, high levels of ATP could activate P2X 7 R in astrocytes and contribute to defects in neurotransmission. The opening of P2X 7 R channels allows calcium influx which modulates the release of... More
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Endless fates most bountiful  The spectrum of possible duplicated gene fate...
Published: 30 November 2022
Figure 1 Endless fates most bountiful The spectrum of possible duplicated gene fates is depicted according to the functional similarity between paralogues, where complete functional redundancy (far left) represents that the greatest degree of functional similarity that can be exhibited and pseudo... More
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Protein interactions range from ordered to disordered binding modes  ( A ) ...
Published: 23 November 2022
Figure 1 Protein interactions range from ordered to disordered binding modes ( A ) Structural order and contact patterns of the bound complex. In ordered binding modes, represented by the complex of p53 tumor suppressor (blue) with Mdm2 (gray, PDB: 2MWY, [ 12 ]), the binding interface is well-def... More
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Protein interactions sample multiplicity of binding modes (MBM)  Protein in...
Published: 23 November 2022
Figure 2 Protein interactions sample multiplicity of binding modes (MBM) Protein interactions with low MBM sample only one binding mode (unimodal), which can be ordered (blue, p53/Mdm2 complex [ 12 ]) or disordered (orange, Gcn4/Med15 complex [ 18 ]). Context-dependent protein interactions have h... More
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The droplet landscape indicates an impact of ALS-associated mutations on th...
Published: 23 November 2022
Figure 3 The droplet landscape indicates an impact of ALS-associated mutations on the multiplicity of binding modes (MBM) The droplet landscape represents the change in the cellular state as a function of MBM (x-axis) and droplet-promoting probability p DP (y-axis) in ALS-associated mutations ... More
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Energetic frustration in specific protein complexes  Structures for transla...
Published: 23 November 2022
Figure 4 Energetic frustration in specific protein complexes Structures for translation initiation factor 2 (eIF2g) subunit gamma in complex with alpha and beta (PDB: 3CW2 [ 66 ], upper left) and in complex with a substrate-mimicking small molecule (PDB 3I1F; lower right). The disordered binding ... More
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Schematic highlighting key principles governing discrete, dynamic complexes...
Published: 23 November 2022
Figure 1 Schematic highlighting key principles governing discrete, dynamic complexes of IDRs and dynamic, condensed phases of IDRs with exchanging interactions ( A ) Biophysical model for the discrete, dynamic complex formed by Sic1 and the WD40 domain of Cdc4. Multisite phosphorylation of Sic1 (... More
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Spectrum of conformational disorder  A whole spectrum of disorder can occur...
Published: 23 November 2022
Figure 1 Spectrum of conformational disorder A whole spectrum of disorder can occur in proteins, from completely unstructured sequences to disordered linkers and tails flanking folded domains or just short loops that introduce local disorder in mostly folded proteins. In addition, given the lack ... More
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Single-molecule fluorescence spectroscopy  ( A ) In Förster resonance energ...
Published: 23 November 2022
Figure 2 Single-molecule fluorescence spectroscopy ( A ) In Förster resonance energy transfer (FRET), donor excitation can either result in a photon emission from the donor itself or a nonradiative energy transfer to the acceptor with consequent emission of an acceptor photon without a direct exc... More
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Experimental methods for the study of disordered proteins  Single-molecule ...
Published: 23 November 2022
Figure 3 Experimental methods for the study of disordered proteins Single-molecule fluorescence offers a versatile set of tools for the investigation of conformations and dynamics in IDPs and IDRs. FCS provides access to the diffusion time τ diff and corresponding hydrodynamic radius R H (s... More
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Examples of single-molecule fluorescence measurements  ( A ) Measurements o...
Published: 23 November 2022
Figure 4 Examples of single-molecule fluorescence measurements ( A ) Measurements of the interdye distance (represented in terms of apparent radius of gyration) as function of interdye sequence separation for the unfolded state of two proteins, human CyclophilinA (hCyp) and Cold-shock protein fro... More
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Structure, sequence of α-Syn, and its aggregation  ( A ) Schematic represen...
Published: 14 November 2022
Figure 1 Structure, sequence of α-Syn, and its aggregation ( A ) Schematic representation depicting three distinct domains of α-Syn: amphipathic N-terminus (residue 1-60), hydrophobic and aggregation prone NAC (residue 61-95) and acidic C-terminus (residue 96-140). N- terminus is majorly the muta... More
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α-Syn assemblies formed during the aggregation process  The aggregation pat...
Published: 14 November 2022
Figure 2 α-Syn assemblies formed during the aggregation process The aggregation pathway of α-Syn underlies self-assembly of monomeric protein into amyloid fibrils via various intermediate species. The natively unstructured protein multimerizes into oligomers of heterogeneous sizes and morphologie... More
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Liquid–liquid phase separation and subsequent solidification of α-Syn  ( A ...
Published: 14 November 2022
Figure 3 Liquid–liquid phase separation and subsequent solidification of α-Syn ( A ) Schematic representation of the sequential events underlying α-Syn aggregation via LLPS in a pathological relevant milieu. The monomeric protein undergoes de-mixing in presence of extrinsic factors (crowder, salt... More
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Variation in  Bone morphogenetic protein 4  and  calmodulin  specify variat...
Published: 14 November 2022
Figure 1 Variation in Bone morphogenetic protein 4 and calmodulin specify variation in beak morphology ( A ) Variation in beak width (W) and depth (D) is correlated with Bone morphogenetic protein 4 ( Bmp4 ) expression level and expression timing (blue), and variation in beak length is corr... More
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Variation in  tartan  expression level, timing, and localization specifies ...
Published: 14 November 2022
Figure 2 Variation in tartan expression level, timing, and localization specifies variation in clasper morphology ( A ) The four species of the Drosophila melanogaster species complex possess species-specific differences in the size and shape of male genital structures. Left: A representation... More
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Schematic showing the major regions in the tau primary sequence  This shows...
Published: 14 November 2022
Figure 1 Schematic showing the major regions in the tau primary sequence This shows the two possible N terminal domains (N1, N2), two proline rich regions (P1, P2) and the imperfect repeat regions or microtubule binding regions: R1 (243-273), R2 (274-304), R3 (305-335) and R4 (336-367). Tau can e... More
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The structure of tau bound to microtubules  Structure of microtubules showi...
Published: 14 November 2022
Figure 2 The structure of tau bound to microtubules Structure of microtubules showing the binding of tau between molecules solved using cryoEM [ 16 ] ( 6CVK .pdb). Insert shows the extended conformation of tau when it is associated with microtubules. More
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The morphology of paired helical filaments formed by tau  in vivo  and  in ...
Published: 14 November 2022
Figure 3 The morphology of paired helical filaments formed by tau in vivo and in vitro . Left and middle panel show immunogold labelling electron microscopy of tau filaments in AD brain tissue (tau filaments identified using antibodies against total tau ( A ) and tau oligomers (T22) ( B ) whil... More
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Structures of tau  CryoEM structures for tauopathy derived filaments showin...
Published: 14 November 2022
Figure 4 Structures of tau CryoEM structures for tauopathy derived filaments showing the conformation of the building blocks viewed down the fibre axis using spheres for the atoms. ( A ) Straight filaments (SF) from AD brain [ 48 ] (6HRF), filaments from cortical basal degeneration [ 49 ] (6TJX),... More
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Comparison of the structures of tau fragments formed  in vitro   CryoEM str...
Published: 14 November 2022
Figure 5 Comparison of the structures of tau fragments formed in vitro CryoEM structures for tau297-391, dGAE and 266/297-391 [ 54 ] assembled under a wide variety of conditions. Listed conditions refer to those entered in table 1 of Lövestam et al. [ 54 ] and identified by conditions in bracke... More
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A potential pathway to tau amyloid  Schematic image showing the potential f...
Published: 14 November 2022
Figure 6 A potential pathway to tau amyloid Schematic image showing the potential for transition from liquid–liquid phase separation to solid phase amyloid fibrils in liquid droplets in cells and showing coacervation driven by charge-charge interactions between tau (red) and RNA (blue). More
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Prevalence of IDPs and MLOs  ( A ) Grows of the IDP- and MLO-related public...
Published: 09 November 2022
Figure 1 Prevalence of IDPs and MLOs ( A ) Grows of the IDP- and MLO-related publications illustrated by the results of a simple bibliometric analysis, where the PubMed database was used to look at the papers dealing with disorder- and MLO-related topics. Search terms for the IDP-related papers i... More
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Intrinsic disorder status of proteins found in human MLOs  Comparison of me...
Published: 09 November 2022
Figure 2 Intrinsic disorder status of proteins found in human MLOs Comparison of mean disorder scores (MDS) evaluated for each protein by PONDR® VSL2 and PONDR® FIT. Data for proteins in individual MLOs are shown by different symbols and colors (see keys in the figure). Larger values correspond t... More
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Structural transitions are also dynamic transitions  ( A ) Coarse-grained b...
Published: 09 November 2022
Figure 1 Structural transitions are also dynamic transitions ( A ) Coarse-grained biomolecular simulations show that proteins with a multidomain architecture (like FUS) could assemble into structures with varying degrees of order, including disordered fully mixed condensates, core–shell droplets,... More
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Loss of intercluster dynamics leads to arrested coalescence  Multidomain RN...
Published: 09 November 2022
Figure 2 Loss of intercluster dynamics leads to arrested coalescence Multidomain RNA-binding proteins can exist in several self-assembled states, which could be single- or multiphase. Multiphase condensates can seed order via strong homotypic interactions between prion-like, low-complexity domain... More
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Aging in stickers-and-spacers polymer self-assemblies  For concentrations e...
Published: 09 November 2022
Figure 3 Aging in stickers-and-spacers polymer self-assemblies For concentrations exceeding the phase-separation threshold, stickers-and-spacers polymers self-assemble into dense, biopolymer-rich compartments. Nascent droplets are stabilized by several transient interactions. As these droplets ag... More
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Effects of phosphorylation of IDPs on chemistry  ( A ) Chemical structure, ...
Published: 09 November 2022
Figure 1 Effects of phosphorylation of IDPs on chemistry ( A ) Chemical structure, volume, and p K a for Ser, Thr, and Tyr as well as for pSer, pThr, and pTyr. ( B ) Differences in backbone secondary chemical shift distributions between the phosphorylated and non-phosphorylated amino acids (lef... More
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Effects of phosphorylation of IDPs on the structure and ensembles  ( A ) St...
Published: 09 November 2022
Figure 2 Effects of phosphorylation of IDPs on the structure and ensembles ( A ) Structural effects upon phosphorylation of IDPs. Secondary structure stabilization (top), destabilization (second row), proline cis-trans isomerization (third row) and global folding (bottom). ( B ) Global conforma... More
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Effects of phosphorylation of IDPs on function  Functional effects of IDP p...
Published: 09 November 2022
Figure 3 Effects of phosphorylation of IDPs on function Functional effects of IDP phosphorylation (left) with graphical schematics of the resulting biological output (right). ( A ) On/Off switch by single phosphorylation resulting in helix unfolding [ 35 , 60 ] or ( B ) compaction [ 42 ]. ( C )... More
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The p53 corkboard  Anecdotally, the protector of the genome may acquire add...
Published: 09 November 2022
Figure 2 The p53 corkboard Anecdotally, the protector of the genome may acquire additional tasks inside a p53’s researcher office. ( A ) The p53 TAD and the CTD are low-ordered domains assuming an ensemble of conformations like the tail and the tongue of the chameleon. The DBD is the chameleon bo... More
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Experimental evidence of the p53 chameleonic compositions  ( A ) Confocal i...
Published: 09 November 2022
Figure 3 Experimental evidence of the p53 chameleonic compositions ( A ) Confocal images showing the p53-DBD forming LLPS and the mutant p53-DBD-M237I forming solid-like PT in vitro . Cell experiments show full-length mutant p53-M237I forming LLPS inside the nucleolus (adapted from [ 45 ]). ( B ... More
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Schematic structures of glycans that are utilized by butyrogenic bacteria  ...
Published: 09 November 2022
Figure 1 Schematic structures of glycans that are utilized by butyrogenic bacteria ( A ) Xylan, ( B ) Starch, ( C ) Inulin, and ( D ) Mannan are from plants. ( E ) The human milk oligosaccharides LNT (lacto- N -tetraose), LNFP-II (lacto- N -fucopentaose II), LNDFH-II (lacto- N -difucohexaose II),... More
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Overview of experimentally described glycan utilization by selected model H...
Published: 09 November 2022
Figure 2 Overview of experimentally described glycan utilization by selected model HGM strains Only biochemically characterized extracellular glycoside hydrolases and transport binding proteins that confer glycan breakdown and uptake of oligomeric products, respectively, are shown. For simplicity... More
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Crystal structures of selected previously unknown CAZyme activities or foun...
Published: 09 November 2022
Figure 3 Crystal structures of selected previously unknown CAZyme activities or founding members of newly established CAZy families from butyrogenic bacteria ( A ) The crystal structure of the N-terminal xylan binding module from the multi-modular GH10 xylanase from R. intestinalis (PDB: 6SGF ... More