Journal of Structural Biology

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  • Crystal structure of the extracellular juxtamembrane region of Robo1
    [Apr 2014]

    Publication date: Available online 6 March 2014
    Source:Journal of Structural Biology

    Author(s): Reut Barak , Roxane Lahmi , Lada Gevorkyan-Airapetov , Eliad Levy , Amit Tzur , Yarden Opatowsky

    Robo receptors play pivotal roles in neurodevelopment, and their deregulation is implicated in several neuropathological conditions and cancers. To date, the mechanism of Robo activation and regulation remains obscure. Here we present the crystal structure of the juxtamembrane (JM) domains of human Robo1. The structure exhibits unexpectedly high backbone similarity to the netrin and RGM binding region of neogenin and DCC, which are functionally related receptors of Robo1. Comparison of these structures reveals a conserved surface that overlaps with a cluster of oncogenic and neuropathological mutations found in all Robo isoforms. The structure also reveals the intricate folding of the JM linker, which points to its role in Robo1 activation. Further experiments with cultured cells demonstrate that exposure or relief of the folded JM linker results in enhanced shedding of the Robo1 ectodomain.





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  • Cover 2 - Editorial Board
    [Apr 2014]

    Publication date: March 2014
    Source:Journal of Structural Biology, Volume 185, Issue 3









    Categories: Journal Articles
  • Table of Contents / barcode
    [Apr 2014]

    Publication date: March 2014
    Source:Journal of Structural Biology, Volume 185, Issue 3









    Categories: Journal Articles
  • Super-resolution imaging of Escherichia coli nucleoids reveals highly structured and asymmetric segregation during fast growth
    [Apr 2014]

    Publication date: March 2014
    Source:Journal of Structural Biology, Volume 185, Issue 3

    Author(s): Christoph Spahn , Ulrike Endesfelder , Mike Heilemann

    Bacterial replication and chromosome segregation are highly organized both in space and in time. However, spatial analysis is hampered by the resolution limit of conventional fluorescence microscopy. In this study, we incubate rapidly-growing Escherichia coli with 5-ethynyl-2′-deoxyuridine (EdU), label the resulting EdU-DNA with photoswitchable fluorophores, and image incorporated molecules with an average experimental precision of 13nm. During the segregation process, nucleoids develop highly-defined and cell-cycle dependent hetero-structures, which contain discrete DNA fibers with diameters far below the diffraction limit. Strikingly, these structures appear temporally shifted between sister chromosomes, an asymmetry which accumulates for ongoing replication rounds. Moreover, nucleoid positioning and expansion along the bacterial length axis fit into an elongation-mediated segregation model in fast growing E. coli cultures. This is supported by close proximity of the nucleoids to the bacterial plasma membrane, the nature of the observed hetero-structures and recently found interactions of membrane-associated proteins with DNA.





    Categories: Journal Articles
  • Exploiting radiation damage to map proteins in nucleoprotein complexes: The internal structure of bacteriophage T7
    [Apr 2014]

    Publication date: March 2014
    Source:Journal of Structural Biology, Volume 185, Issue 3

    Author(s): Naiqian Cheng , Weimin Wu , Norman R. Watts , Alasdair C. Steven

    In the final stage of radiation damage in cryo-electron microscopy of proteins, bubbles of hydrogen gas are generated. Proteins embedded in DNA bubble sooner than free-standing proteins and DNA does not bubble under the same conditions. These properties make it possible to distinguish protein from DNA. Here we explored the scope of this technique (“bubblegram imaging”) by applying it to bacteriophage T7, viewed as a partially defined model system. T7 has a thin-walled icosahedral capsid, 60nm in diameter, with a barrel-shaped protein core under one of its twelve vertices (the portal vertex). The core is densely wrapped with DNA but details of their interaction and how their injection into a host bacterium is coordinated are lacking. With short (10s) intervals between exposures of 17electrons/Å2 each, bubbling starts in the third exposure, with 1–4 bubbles nucleating in the core: in subsequent exposures, these bubbles grow and merge. A 3D reconstruction from fifth-exposure images depicts a bipartite cylindrical gas cloud in the core. In its portal-proximal half, the axial region is gaseous whereas in the portal-distal half, it is occupied by a 3nm-wide dense rod. We propose that they respectively represent core protein and an end of the packaged genome, poised for injection into a host cell. Single bubbles at other sites may represent residual scaffolding protein. Thus, bubbling depends on dose rate, protein amount, and tightness of the DNA seal.





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  • Structural and mechanistic insights into the kynurenine aminotransferase-mediated excretion of kynurenic acid
    [Apr 2014]

    Publication date: March 2014
    Source:Journal of Structural Biology, Volume 185, Issue 3

    Author(s): Ken Okada , Clement Angkawidjaja , Yuichi Koga , Shigenori Kanaya

    Kynurenine aminotransferase (KAT) is a homodimeric pyridoxal protein that mediates the catalytic conversion of kynurenine (KYN) to kynurenic acid (KYA), an endogenous N-methyl-d-aspartate (NMDA) receptor antagonist. KAT is involved in the biosynthesis of glutamic and aspartic acid, functions as a neurotransmitter for the NMDA receptor in mammals, and is regulated by allosteric mechanisms. Its importance in various diseases such as schizophrenia makes KAT a highly attractive drug target. Here, we present the crystal structure of the Pyrococcus horikoshii KAT (PhKAT) in complex with pyridoxamine phosphates (PMP), KYN, and KYA. Surprisingly, the PMP was bound to the LYS-269 of phKAT by forming a covalent hydrazine bond. This crystal structure clearly shows that an amino group of KYN was transaminated to PLP, which forms a Schiff’s base with the LYS-269 of the KYN. Thus, our structure confirms that the PMPs represent an intermediate state during the KAT reaction. Thus, PhKAT catalyzes the sequential conversion of KYN to KYA via the formation of an intermediate 4-(2-aminophenyl)-2,4-dioxobutanoate (4AD), which is spontaneously converted to KYA in the absence of an amino group acceptor. Furthermore, we identified the two entry and exit sites of the PhKAT homodimer for KYN and KYA, respectively. The structural data on PhKAT presented in this manuscript contributes to further the understanding of transaminase enzyme reaction mechanisms.





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  • Single particle 3D reconstruction for 2D crystal images of membrane proteins
    [Apr 2014]

    Publication date: March 2014
    Source:Journal of Structural Biology, Volume 185, Issue 3

    Author(s): Sebastian Scherer , Marcel Arheit , Julia Kowal , Xiangyan Zeng , Henning Stahlberg

    In cases where ultra-flat cryo-preparations of well-ordered two-dimensional (2D) crystals are available, electron crystallography is a powerful method for the determination of the high-resolution structures of membrane and soluble proteins. However, crystal unbending and Fourier-filtering methods in electron crystallography three-dimensional (3D) image processing are generally limited in their performance for 2D crystals that are badly ordered or non-flat. Here we present a single particle image processing approach, which is implemented as an extension of the 2D crystallographic pipeline realized in the 2dx software package, for the determination of high-resolution 3D structures of membrane proteins. The algorithm presented, addresses the low single-to-noise ratio (SNR) of 2D crystal images by exploiting neighborhood correlation between adjacent proteins in the 2D crystal. Compared with conventional single particle processing for randomly oriented particles, the computational costs are greatly reduced due to the crystal-induced limited search space, which allows a much finer search space compared to classical single particle processing. To reduce the considerable computational costs, our software features a hybrid parallelization scheme for multi-CPU clusters and computer with high-end graphic processing units (GPUs). We successfully apply the new refinement method to the structure of the potassium channel MloK1. The calculated 3D reconstruction shows more structural details and contains less noise than the map obtained by conventional Fourier-filtering based processing of the same 2D crystal images.





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  • Multi-resolution correlative focused ion beam scanning electron microscopy: Applications to cell biology
    [Apr 2014]

    Publication date: March 2014
    Source:Journal of Structural Biology, Volume 185, Issue 3

    Author(s): Kedar Narayan , Cindy M. Danielson , Ken Lagarec , Bradley C. Lowekamp , Phil Coffman , Alexandre Laquerre , Michael W. Phaneuf , Thomas J. Hope , Sriram Subramaniam

    Efficient correlative imaging of small targets within large fields is a central problem in cell biology. Here, we demonstrate a series of technical advances in focused ion beam scanning electron microscopy (FIB–SEM) to address this issue. We report increases in the speed, robustness and automation of the process, and achieve consistent z slice thickness of ∼3nm. We introduce “keyframe imaging” as a new approach to simultaneously image large fields of view and obtain high-resolution 3D images of targeted sub-volumes. We demonstrate application of these advances to image post-fusion cytoplasmic intermediates of the HIV core. Using fluorescently labeled cell membranes, proteins and HIV cores, we first produce a “target map” of an HIV infected cell by fluorescence microscopy. We then generate a correlated 3D EM volume of the entire cell as well as high-resolution 3D images of individual HIV cores, achieving correlative imaging across a volume scale of 109 in a single automated experimental run.





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  • Computational study of the elastic properties of Rheum rhabarbarum tissues via surrogate models of tissue geometry
    [Apr 2014]

    Publication date: March 2014
    Source:Journal of Structural Biology, Volume 185, Issue 3

    Author(s): Tanvir R. Faisal , Nicolay Hristozov , Tamara L. Western , Alejandro D. Rey , Damiano Pasini

    Plant petioles and stems are hierarchical cellular structures, displaying geometrical features defined at multiple length scales. One or more of the intermediate hierarchical levels consists of tissues in which the cellular distribution is quasi-random, a factor that affects the elastic properties of the tissues. The current work focuses on the finite element analysis (FEA) of the constituent tissues of the plant Rheum rhabarbarum (rhubarb). The geometric model is generated via a recently introduced method: the finite edge centroidal Voronoi tessellation (FECVT), which is capable to capture the gradients of cellularity and diversified pattern of cellular materials, as opposed to current approaches in literature. The effective stiffness of the tissues is obtained by using an accurate numerical homogenization technique via detailed finite element analysis of the models of sub-regions of the tissues. As opposed to a large-scale representative volume element (RVE), statistical volume elements (SVE) are considered in this work to model tissue microstructures that are highly random. 2D finite element analyses demonstrate that the distribution of cells in collenchyma and parenchyma tissue make them stiffer in two different directions, while the overall effect of the combined tissues results in approximately equal stiffness in both directions. The rhubarb tissues, on the other hand, are more compliant than periodic and quasi-uniform random cellular materials by a factor of up to 47% and 44%, respectively. The variations of the stiffness shows the stiffening role that cell shape, size, and graded cellular distribution play in the mechanics of the rhubarb tissue.





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  • Automatic cryo-EM particle selection for membrane proteins in spherical liposomes
    [Apr 2014]

    Publication date: March 2014
    Source:Journal of Structural Biology, Volume 185, Issue 3

    Author(s): Yunhui Liu , Fred J. Sigworth

    Random spherically constrained (RSC) single particle reconstruction is a method to obtain structures of membrane proteins embedded in lipid vesicles (liposomes). As in all single-particle cryo-EM methods, structure determination is greatly aided by reliable detection of protein “particles” in micrographs. After fitting and subtraction of the membrane density from a micrograph, normalized cross-correlation (NCC) and estimates of the particle signal amplitude are used to detect particles, using as references the projections of a 3D model. At each pixel position, the NCC is computed with only those references that are allowed by the geometric constraint of the particle’s embedding in the spherical vesicle membrane. We describe an efficient algorithm for computing this position-dependent correlation, and demonstrate its application to selection of membrane-protein particles, GluA2 glutamate receptors, which present very different views from different projection directions.





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  • Correlative Light- and Electron Microscopy with Chemical Tags
    [Apr 2014]

    Publication date: Available online 31 March 2014
    Source:Journal of Structural Biology

    Author(s): Mario Perkovic , Michael Kunz , Ulrike Endesfelder , Stefanie Bunse , Christoph Wigge , Zhou Yu , Victor-Valentin Hodirnau , Margot P. Scheffer , Anja Seybert , Sebastian Malkusch , Erin M. Schuman , Mike Heilemann , Achilleas S. Frangakis

    Correlative microscopy incorporates the specificity of fluorescent protein labeling into high-resolution electron micrographs. Several approaches exist for correlative microscopy, most of which have used the green fluorescent protein (GFP) as the label for light microscopy. Here we use chemical tagging and synthetic fluorophores instead, in order to achieve protein-specific labeling, and to perform multicolor imaging. We show that synthetic fluorophores preserve their post-embedding fluorescence in the presence of uranyl acetate. Post-embedding fluorescence is of such quality that the specimen can be prepared with identical protocols for scanning electron microscopy (SEM) and transmission electron microscopy (TEM); this is particularly valuable when singular or otherwise difficult samples are examined. We show that synthetic fluorophores give bright, well-resolved signals in super-resolution light microscopy, enabling us to superimpose light microscopic images with a precision of up to 25 nm in the x-y plane on electron micrographs. To exemplify the preservation quality of our new method we visualize the molecular arrangement of cadherins in adherens junctions of mouse epithelial cells.





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  • Automated particle correspondence and accurate tilt-axis detection in tilted-image pairs
    [Apr 2014]

    Publication date: Available online 30 March 2014
    Source:Journal of Structural Biology

    Author(s): Maxim Shatsky , Pablo Arbelaez , Bong-Gyoon Han , Dieter Typke , Steven E. Brenner , Jitendra Malik , Robert M. Glaeser

    Tilted electron microscope images are routinely collected for an ab initio structure reconstruction as a part of the Random Conical Tilt (RCT) or Orthogonal Tilt Reconstruction (OTR) methods, as well as for various applications using the “free-hand” procedure. These procedures all require identification of particle pairs in two corresponding images as well as accurate estimation of the tilt-axis used to rotate the Electron Microscope (EM) grid. Here we present a computational approach, PCT (Particle Correspondence from Tilted pairs), based on tilt-invariant context and projection matching that addresses both problems. The method benefits from treating the two problems as a single optimization task. It automatically finds corresponding particle pairs and accurately computes tilt-axis direction even in the cases when EM grid is not perfectly planar.





    Categories: Journal Articles
  • 2dx_automator: Implementation of a Semiautomatic High-Throughput High-Resolution Cryo-Electron Crystallography Pipeline
    [Apr 2014]

    Publication date: Available online 28 March 2014
    Source:Journal of Structural Biology

    Author(s): Sebastian Scherer , Julia Kowal , Mohamed Chami , Venkata Dandey , Marcel Arheit , Philippe Ringler , Henning Stahlberg

    The introduction of direct electron detectors (DED) to cryo-electron microscopy has tremendously increased the signal-to-noise ratio (SNR) and quality of the recorded images. We discuss the optimal use of DEDs for cryo-electron crystallography, introduce a new automatic image processing pipeline, and demonstrate the vast improvement in the resolution achieved by the use of both together, especially for highly tilted samples. The new processing pipeline (now included in the software package 2dx) exploits the high SNR and frame readout frequency of DEDs to automatically correct for beam-induced sample movement, and reliably processes individual crystal images without human interaction as data are being acquired. A new graphical user interface (GUI) condenses all information required for quality assessment in one window, allowing the imaging conditions to be verified and adjusted during the data collection session. With this new pipeline an automatically generated unit cell projection map of each recorded 2D crystal is available less than five minutes after the image was recorded. The entire processing procedure yielded a three-dimensional reconstruction of the 2D-crystallized ion-channel membrane protein Mlok1 with a much-improved resolution of 5Å in-plane and 7Å in the z-direction, within two days of data acquisition and simultaneous processing. The results obtained are superior to those delivered by conventional photographic film-based methodology of the same sample, and demonstrate the importance of drift-correction.





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  • A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein
    [Apr 2014]

    Publication date: Available online 28 March 2014
    Source:Journal of Structural Biology

    Author(s): Emma S. Gleave , Helgo Schmidt , Andrew P. Carter

    Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our S accharomyces cerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins.





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  • Axial helix rotation as a mechanism for signal regulation inferred from the crystallographic analysis of the E. coli serine chemoreceptor
    [Apr 2014]

    Publication date: Available online 27 March 2014
    Source:Journal of Structural Biology

    Author(s): Hedda U. Ferris , Kornelius Zeth , Michael Hulko , Stanislaw Dunin-Horkawicz , Andrei N. Lupas

    Bacterial chemotaxis receptors are elongated homodimeric coiled-coil bundles, which transduce signals generated in an N-terminal sensor domain across 15–20nm to a conserved C-terminal signaling subdomain. This signal transduction regulates the activity of associated kinases, altering the behavior of the flagellar motor and hence cell motility. Signaling is in turn modulated by selective methylation and demethylation of specific glutamate and glutamine residues in an adaptation subdomain. We have determined the structure of a chimeric protein, consisting of the HAMP domain from Archaeoglobus fulgidus Af1503 and the methyl-accepting domain of Escherichia coli Tsr. It shows a 21nm coiled coil that alternates between two coiled-coil packing modes: canonical knobs-into-holes and complementary x-da, a variant form related to the canonical one by axial rotation of the helices. Comparison of the obtained structure to the Thermotoga maritima chemoreceptor TM1143 reveals that they adopt different axial rotation states in their adaptation subdomains. This conformational change is presumably induced by the upstream HAMP domain and may modulate the affinity of the chemoreceptor to the methylation–demethylation system. The presented findings extend the cogwheel model for signal transmission to chemoreceptors.





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  • TRDistiller: A Rapid Filter for Enrichment of Sequence Datasets with Proteins Containing Tandem Repeats
    [Apr 2014]

    Publication date: Available online 26 March 2014
    Source:Journal of Structural Biology

    Author(s): François D. RICHARD , Andrey V. KAJAVA

    The dramatic growth of sequencing data evokes an urgent need to improve bioinformatics tools for large-scale proteome analysis. Over the last two decades, the foremost efforts of computer scientists were devoted to proteins with aperiodic sequences having globular 3D structures. However, a large portion of proteins contain periodic sequences representing arrays of repeats that are directly adjacent to each other (so called tandem repeats or TRs). These proteins frequently fold into elongated fibrous structures carrying different fundamental functions. Algorithms specific to the analysis of these regions are urgently required since the conventional approaches developed for globular domains have had limited success when applied to the TR regions. The protein TRs are frequently not perfect, containing a number of mutations, and some of them cannot be easily identified. To detect such “hidden” repeats several algorithms have been developed. However, the most sensitive among them are time-consuming and, therefore, inappropriate for large scale proteome analysis. To speed up the TR detection we developed a rapid filter that is based on the comparison of composition and order of short strings in the adjacent sequence motifs. Tests show that our filter discards up to 22.5% of proteins which are known to be without TRs while keeping almost all (99.2%) TR-containing sequences. Thus, we are able to decrease the size of the initial sequence dataset enriching it with TR-containing proteins which allows a faster subsequent TR detection by other programs. The program is available upon request.





    Categories: Journal Articles
  • Crystallographic snapshot of the Escherichia coli EnvZ histidine kinase in an active conformation
    [Apr 2014]

    Publication date: Available online 26 March 2014
    Source:Journal of Structural Biology

    Author(s): Hedda U. Ferris , Murray Coles , Andrei N. Lupas , Marcus D. Hartmann

    Sensor histidine kinases are important sensors of the extracellular environment and relay signals via conformational changes that trigger autophosphorylation of the kinase and subsequent phosphorylation of a response regulator. The exact mechanism and the regulation of this protein family are a matter of ongoing investigation. Here we present a crystal structure of a functional chimeric protein encompassing the entire catalytic part of the Escherichia coli EnvZ histidine kinase, fused to the HAMP domain of the Archaeoglobus fulgidus Af1503 receptor. The construct is thus equivalent to the full cytosolic part of EnvZ. The structure shows a putatively active conformation of the catalytic domain and gives insight into how this conformation could be brought about in response to sensory input. Our analysis suggests a sequential flip-flop autokinase mechanism.





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  • Frealix: Model-based refinement of helical filament structures from electron micrographs
    [Apr 2014]

    Publication date: Available online 20 March 2014
    Source:Journal of Structural Biology

    Author(s): Alexis Rohou , Nikolaus Grigorieff

    The structures of many helical protein filaments can be derived from electron micrographs of their suspensions in thin films of vitrified aqueous solutions. The most successful and generally-applicable approach treats short segments of these filaments as independent “single particles”, yielding near-atomic resolution for rigid and well-ordered filaments. The single-particle approach can also accommodate filament deformations, yielding sub-nanometer resolution for more flexible filaments. However, in the case of thin and flexible filaments, such as some amyloid-β (Aβ) fibrils, the single-particle approach may fail because helical segments can be curved or otherwise distorted and their alignment can be inaccurate due to low contrast in the micrographs. We developed new software called Frealix that allows the use of arbitrarily short filament segments during alignment to approximate even high curvatures. All segments in a filament are aligned simultaneously with constraints that ensure that they connect to each other in space to form a continuous helical structure. In this paper, we describe the algorithm and benchmark it against datasets of Aβ(1–40) fibrils and tobacco mosaic virus (TMV), both analyzed in earlier work. In the case of TMV, our algorithm achieves similar results to single-particle analysis. In the case of Aβ(1–40) fibrils, we match the previously-obtained resolution but we are also able to obtain reliable alignments and ∼8-Å reconstructions from curved filaments. Our algorithm also offers a detailed characterization of filament deformations in three dimensions and enables a critical evaluation of the worm-like chain model for biological filaments.





    Categories: Journal Articles
  • Influence of repeat numbers on self-assembly rates of repetitive recombinant spider silk proteins
    [Apr 2014]

    Publication date: Available online 20 March 2014
    Source:Journal of Structural Biology

    Author(s): Martin Humenik , Michael Magdeburg , Thomas Scheibel

    Assembly of recombinant spider silk variants eADF4(Cn) comprising different numbers (n) of the consensus sequence motif C, derived from the natural Araneus diadematus dragline silk ADF4, yielded indistinguishable nanofibrils in cases of n⩾2. The C-module comprises 35 amino acids rich in glycine and proline residues (in GPGXY repeats) and one polyalanine stretch (Ala)8. All variants were found to be intrinsically disordered in solution, and upon fibril formation they converted into a cross-β structure. Heterologous seeding indicated high structural compatibility between the different eADF4(Cn) variants, however, their assembly kinetics differed in dependence of the number of repeats. Kinetic analysis revealed a nucleation-growth mechanism typical for the formation of cross-β-fibrils, with nucleation rates as well as growth rates increasing with increasing numbers of repeats. Strikingly, the single C-module did not self-assemble into fibrils, but upon addition of heterologous seeds fibril growth could be observed. Apparently, interconnecting of at least two C-modules significantly facilitates the structural transformation from a disordered state into β-sheet structures, which is necessary for nucleation and beneficial for fibril growth.





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  • The spectrin family of proteins: A unique coiled-coil fold for various molecular surface properties
    [Apr 2014]

    Publication date: Available online 19 March 2014
    Source:Journal of Structural Biology

    Author(s): Aurélie Nicolas , Olivier Delalande , Jean-François Hubert , Elisabeth Le Rumeur

    The spectrin superfamily is composed of proteins involved in cytolinker functions. Their main structural feature is a large central subdomain with numerous repeats folded in triple helical coiled-coils. Their similarity of sequence was considered to be low without detailed quantification of the intra- and intermolecular levels. Among the superfamily, we considered as essential to propose an overview of the surface properties of all the repeats of the five proteins of the spectrin family, namely α- and β-spectrins, α-actinin, dystrophin and utrophin. Therefore, the aim of this work was to obtain a quantitative comparison of all the repeats at both the primary sequence and the three-dimensional levels. For that purpose, we applied homology modelling methods to obtain structural models for successive and overlapping tandem repeats of the human erythrocyte α- and β-spectrins and utrophin, as previously undertaken for dystrophin, and we used the known structure of α-actinin. The matrix calculation of the pairwise similarities of all the repeat sequences and the electrostatic and hydrophobic surface properties throughout the protein family support the view that spectrins and α-actinin on one hand and utrophin and dystrophin on the other hand share some structural similarities, but a detailed molecular characterisation highlights substantial differences. The repeats within the family are far from identical, which is consistent with their multiple interactions with different cellular partners, including proteins and membrane lipids.





    Categories: Journal Articles