Journal of Structural Biology

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  • TRDistiller: A rapid filter for enrichment of sequence datasets with proteins containing tandem repeats
    [Jun 2014]

    Publication date: June 2014
    Source:Journal of Structural Biology, Volume 186, Issue 3

    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 methods. The program is available upon request.





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

    Publication date: June 2014
    Source:Journal of Structural Biology, Volume 186, Issue 3

    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
  • Convergently-evolved structural anomalies in the coiled coil domains of insect silk proteins
    [Jun 2014]

    Publication date: June 2014
    Source:Journal of Structural Biology, Volume 186, Issue 3

    Author(s): Tara D. Sutherland , Holly E. Trueman , Andrew A. Walker , Sarah Weisman , Peter M. Campbell , Zhaoming Dong , Mickey G. Huson , Andrea L. Woodhead , Jeffrey S. Church

    The use of coiled coil proteins as the basis of silk materials is an engineering solution that has evolved convergently in at least five insect lineages—the stinging hymenopterans (ants, bees, hornets), argid sawflies, fleas, lacewings, and praying mantises—and persisted throughout large radiations of these insect families. These coiled coil silk proteins share a characteristic distinct from other coiled coil proteins, in that they are fabricated into solid materials after accumulating as highly concentrated solutions within dedicated glands. Here, we relate the amino acid sequences of these proteins to the secondary and tertiary structural information available from biophysical methods such as X-ray scattering, nuclear magnetic resonance and Raman spectroscopy. We investigate conserved and convergently evolved features within these proteins and compare these to the features of classic coiled coil proteins including tropomyosin and leucine zippers. Our analysis finds that the coiled coil domains of insect silk proteins have several common structural anomalies including a high prevalence of alanine residues in core positions. These atypical features of the coiled coil fibrous proteins – which likely produce deviations from canonical coiled-coil structure – likely exist due to selection pressures related to the process of silk fabrication and the final function of the proteins.





    Categories: Journal Articles
  • Effect of sequence features on assembly of spider silk block copolymers
    [Jun 2014]

    Publication date: June 2014
    Source:Journal of Structural Biology, Volume 186, Issue 3

    Author(s): Olena S. Tokareva , Shangchao Lin , Matthew M. Jacobsen , Wenwen Huang , Daniel Rizzo , David Li , Marc Simon , Cristian Staii , Peggy Cebe , Joyce Y. Wong , Markus J. Buehler , David L. Kaplan

    Bioengineered spider silk block copolymers were studied to understand the effect of protein chain length and sequence chemistry on the formation of secondary structure and materials assembly. Using a combination of in vitro protein design and assembly studies, we demonstrate that silk block copolymers possessing multiple repetitive units self-assemble into lamellar microstructures. Additionally, the study provides insights into the assembly behavior of spider silk block copolymers in concentrated salt solutions.





    Categories: Journal Articles
  • Decoration of silk fibroin by click chemistry for biomedical application
    [Jun 2014]

    Publication date: June 2014
    Source:Journal of Structural Biology, Volume 186, Issue 3

    Author(s): Hongshi Zhao , Eva Heusler , Gabriel Jones , Linhao Li , Vera Werner , Oliver Germershaus , Jennifer Ritzer , Tessa Luehmann , Lorenz Meinel

    Silkfibroin (SF) has an excellent biocompatibility and its remarkable structure translates into exciting mechanical properties rendering this biomaterial particularly fascinating for biomedical application. To further boost the material’s biological/preclinical impact, SF is decorated with biologics, typically by carbodiimide/N-hydroxysuccinimide coupling (EDC/NHS). For biomedical application, this chemistry challenges the product risk profile due to the formation of covalent aggregates, particularly when decoration is with biologics occurring naturally in humans as these aggregates may prime for autoimmunity. Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC; click chemistry) provides the necessary specificity to avoid such intermolecular, covalent aggregates. We present a blueprint outlining the necessary chemistry rendering SF compatible with CuAAC and with a particular focus on structural consequences. For that, the number of SF carboxyl groups (carboxyl-SF; required for EDC/NHS chemistry) or azido groups (azido-SF; required for click chemistry) was tailored by means of diazonium coupling of the SF tyrosine residues. Structural impact on SF and decorated SF was characterized by Fourier transform infrared spectroscopy (FTIR). The click chemistry yielded a better controlled product as compared to the EDC/NHS chemistry with no formation of inter- and intramolecular crosslinks as demonstrated for SF decorated with fluorescent model compounds or a biologic, fibroblast growth factor 2 (FGF2), respectively. In conclusion, SF can readily be translated into a scaffold compatible with click chemistry yielding decorated products with a better risk profile for biomedical application.





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

    Publication date: June 2014
    Source:Journal of Structural Biology, Volume 186, Issue 3

    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.





    Categories: Journal Articles
  • A first census of collagen interruptions: Collagen’s own stutters and stammers
    [Jun 2014]

    Publication date: June 2014
    Source:Journal of Structural Biology, Volume 186, Issue 3

    Author(s): Jordi Bella

    The repetitive Gly-X-Y sequence is the telltale sign of triple helical domains in collagens and collagen-like proteins. Most collagen sequences contain sporadic interruptions of this pattern, which may have functional roles in molecular flexibility, assembly or molecular recognition. However, the structural signatures of the different interruptions are not well defined. Here, a first comprehensive survey of collagen interruptions on collagen sequences from different taxonomic groups is presented. Amino acid preferences at the sites of interruption and the flanking triplets are analysed separately for metazoan and prokaryotic collagens and the concept of commensurateness between interruptions is introduced. Known structural information from model peptides is used to present a common framework for hydrogen bonding topology and variations in superhelical twist for the different types of interruptions. Several collagen interruptions are further classified here as stutters or stammers in analogy to the heptad breaks observed in alpha-helical coiled coils, and the structural consequences of commensurate interruptions in heterotrimeric collagens are briefly discussed. Data presented here will be useful for further investigation on the relation between structure and function of collagen interruptions.





    Categories: Journal Articles
  • Bacterial collagen-like proteins that form triple-helical structures
    [Jun 2014]

    Publication date: June 2014
    Source:Journal of Structural Biology, Volume 186, Issue 3

    Author(s): Zhuoxin Yu , Bo An , John A.M. Ramshaw , Barbara Brodsky

    A large number of collagen-like proteins have been identified in bacteria during the past 10years, principally from analysis of genome databases. These bacterial collagens share the distinctive Gly-Xaa-Yaa repeating amino acid sequence of animal collagens which underlies their unique triple-helical structure. A number of the bacterial collagens have been expressed in Escherichia coli, and they all adopt a triple-helix conformation. Unlike animal collagens, these bacterial proteins do not contain the post-translationally modified amino acid, hydroxyproline, which is known to stabilize the triple-helix structure and may promote self-assembly. Despite the absence of collagen hydroxylation, the triple-helix structures of the bacterial collagens studied exhibit a high thermal stability of 35–39°C, close to that seen for mammalian collagens. These bacterial collagens are readily produced in large quantities by recombinant methods, either in the original amino acid sequence or in genetically manipulated sequences. This new family of recombinant, easy to modify collagens could provide a novel system for investigating structural and functional motifs in animal collagens and could also form the basis of new biomedical materials with designed structural properties and functions.





    Categories: Journal Articles
  • Nano-thrombelastography of fibrin during blood plasma clotting
    [Jun 2014]

    Publication date: June 2014
    Source:Journal of Structural Biology, Volume 186, Issue 3

    Author(s): Tímea Feller , Miklós S.Z. Kellermayer , Balázs Kiss

    Hemostasis is a complex process that relies on the sensitive balance between the formation and breakdown of the thrombus, a three-dimensional polymer network of the fibrous protein fibrin. Neither the details of the fibrinogen–fibrin transition, nor the exact mechanisms of fibrin degradation are fully understood at the molecular level. In the present work we investigated the nanoscale-changes in the viscoelasticity of the 3D-fibrin network during fibrinogenesis and streptokinase (STK)-induced fibrinolysis by using a novel application of force spectroscopy, named nano-thrombelastography. In this method the changes in the bending of an oscillating atomic-force-microscope (AFM) cantilever in human blood–plasma droplet were followed as a function of time. Whereas the global features of the time-dependent change in cantilever deflection corresponded well to a macroscopic thrombelastogram, the underlying force spectra revealed large, sample-dependent oscillations in the range of 3–50nN and allowed the separation of elastic and viscous components of fibrin behavior. Upon STK treatment the nano-thrombelastogram signal decayed gradually. The decay was driven by a decrease in thrombus elasticity, whereas thrombus viscosity decayed with a time delay. In scanning AFM images mature fibrin appeared as 17-nm-high and 12–196-nm-wide filaments. STK-treatment resulted in the decrease of filament height and the appearance of a surface roughness with 23.7nm discrete steps that corresponds well to the length of a fibrinogen monomer. Thus, the initial decay of thrombus elasticity during fibrinolysis may be caused by the axial rupture of fibrin fibers.





    Categories: Journal Articles
  • Stretching desmin filaments with receding meniscus reveals large axial tensile strength
    [Jun 2014]

    Publication date: June 2014
    Source:Journal of Structural Biology, Volume 186, Issue 3

    Author(s): Balázs Kiss , Miklós S.Z. Kellermayer

    Desmin forms the intermediate filament system of muscle cells where it plays important role in maintaining mechanical integrity and elasticity. Although the importance of intermediate-filament elasticity in cellular mechanics is being increasingly recognized, the molecular basis of desmin’s elasticity is not fully understood. We explored desmin elasticity by molecular combing with forces calculated to be as large as 4nN. Average filament contour length increased 1.55-fold axial on average. Molecular combing together with EGTA-treatment caused the fragmentation of the filament into short, 60 to 120-nm-long and 4-nm-wide structures. The fragments display a surface periodicity of 38nm, suggesting that they are composed of laterally attached desmin dimers. The axis of the fragments may deviate significantly from that of the overstretched filament, indicating that they have a large orientational freedom in spite of being axially interconnected. The emergence of protofibril fragments thus suggests that the interconnecting head or tail domains of coiled-coil desmin dimers are load-bearing elements during axial stretch.





    Categories: Journal Articles
  • Reprint of: Keratin intermediate filaments: Differences in the sequences of the Type I and Type II chains explain the origin of the stability of an enzyme-resistant four-chain fragment
    [Jun 2014]

    Publication date: June 2014
    Source:Journal of Structural Biology, Volume 186, Issue 3

    Author(s): R.D. Bruce Fraser , David A.D. Parry

    Previous studies have shown that a strong interaction exists between oppositely directed 1B molecular segments in the intermediate filaments of trichocyte keratins. A similar interaction has been identified as having a significant role in the formation of unit-length filaments, a precursor to intermediate filament formation. The present study is concerned with the spatial relationship of these interacting segments and its dependence on differences in the amino acid sequences of the two-chain regions that constitute the 1B molecular segment. It is shown that along a particular line of contact both chain segments possess an elevated concentration of residues with a high propensity for dimer formation. The transition from the reduced to the oxidized state involves a simple axial displacement of one molecular segment relative to the other, with no attendant rotation of either segment. This changes the inter-relationship of the two 1B molecular segments from a loosely packed form to a more compact one. After the slippage eight of the cysteine residues in the dimer are precisely aligned to link up and form the disulfide linkages as observed. The two remaining cysteine residues are located on the outside of the dimer and are presumably involved in inter-dimer bonding. The existence of a unique line of contact requires that two chains in the molecule have different amino acid compositions with the clustering of dimer-favoring residues phased by half the pitch length of the coiled coil.





    Categories: Journal Articles
  • Serial block-face scanning electron microscopy for three-dimensional analysis of morphological changes in mitochondria regulated by Cdc48p/p97 ATPase
    [Jun 2014]

    Publication date: Available online 1 June 2014
    Source:Journal of Structural Biology

    Author(s): Naoyuki Miyazaki , Masatoshi Esaki , Teru Ogura , Kazuyoshi Murata

    Cdc48p is a highly conserved cytosolic AAA chaperone that is involved in a wide range of cellular processes. It consists of two ATPase domains (D1 and D2), with regulatory regions at the N- and C-terminals. We have recently shown that Cdc48p regulates mitochondrial morphology, in that a loss of the ATPase activity or positive cooperativity in the D2 domain leads to severe fragmentations and aggregations of mitochondria in the cytoplasm. We have now used serial block-face scanning electron microscopy (SBF-SEM), an advanced three-dimensional (3D) electron microscopic technique to examine the structures and morphological changes of mitochondria in the yeast Saccharomyces cerevisiae. We found that mutants lacking ATPase activity of Cdc48p showed mitochondrial fragmentations and aggregations, without fusion of the outer membrane. This suggests that the ATPase activity of Cdc48p is necessary for fusion of the outer membranes of mitochondria. Our results also show that SBF-SEM has considerable advantages in morphological and quantitative studies on organelles and intracellular structures in entire cells.





    Categories: Journal Articles
  • Structural investigation of the interaction between the tandem SH3 domains of c-Cbl-associated protein and vinculin
    [Jun 2014]

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

    Author(s): Debiao Zhao , Xuejuan Wang , Junhui Peng , Chongyuan Wang , Fudong Li , Qianqian Sun , Yibo Zhang , Jiahai Zhang , Gang Cai , Xiaobing Zuo , Jihui Wu , Yunyu Shi , Zhiyong Zhang , Qingguo Gong

    c-Cbl-associated protein (CAP) is an important cytoskeletal adaptor protein involved in the regulation of adhesion turnover. The interaction between CAP and vinculin is critical for the recruitment of CAP to focal adhesions. The tandem SH3 domains (herein termed SH3a and SH3b) of CAP are responsible for its interaction with vinculin. However, the structural mechanism underlying the interaction between CAP and vinculin is poorly understood. In this manuscript, we report the solution structure of the tandem SH3 domains of CAP. Our NMR and ITC data indicate that the SH3a and SH3b domains of CAP simultaneously bind to a long proline-rich region of vinculin with different binding specificities. Furthermore, the crystal structures of the individual SH3a and SH3b domains complexed with their substrate peptides indicate that Q807SH3a and D881SH3b are the critical residues determining the different binding specificities of the SH3 domains. Based on the obtained structural information, a model of the SH3ab-vinculin complex was generated using MD simulation and SAXS data.





    Categories: Journal Articles
  • Corrigendum to “A simple Fourier filter for suppression of the missing wedge ray artefacts in single-axis electron tomographic reconstructions” [J. Struct. Biol. 186(1) (2014) 141–152]
    [Jun 2014]

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

    Author(s): Lubomír Kováčik , Sami Kereïche , Johanna L. Höög , Pavel Jůda , Pavel Matula , Ivan Raška







    Categories: Journal Articles
  • Heparin induced dimerization of APP is primarily mediated by E1 and regulated by its acidic domain
    [Jun 2014]

    Publication date: Available online 22 May 2014
    Source:Journal of Structural Biology

    Author(s): Sandra Hoefgen , Ina Coburger , Dirk Roeser , Yvonne Schaub , Sven O. Dahms , Manuel E. Than

    The amyloid precursor protein (APP) and its cellular processing are believed to be centrally involved in the etiology of Alzheimer’s disease (AD). In addition, many physiological functions have been described for APP, including a role in cell–cell- and cell–ECM-adhesion as well as in axonal outgrowth. We show here the molecular determinants of the oligomerization/dimerization of APP, which is central for its cellular (mis)function. Using size exclusion chromatography (SEC), dynamic light scattering and SEC-coupled static light scattering we demonstrate that the dimerization of APP is energetically induced by a heparin mediated dimerization of the E1 domain, which results in a dimeric interaction of E2. We also show that the acidic domain (AcD) interferes with the dimerization of E1 and propose a model where both, cis- and trans-dimerization occur dependent on cellular localization and function.





    Categories: Journal Articles
  • M-free: Scoring the reference bias in sub-tomogram averaging and template matching
    [Jun 2014]

    Publication date: Available online 22 May 2014
    Source:Journal of Structural Biology

    Author(s): Zhou Yu , Achilleas S. Frangakis

    Cryo-electron tomography provides a snapshot of the cellular proteome. With template matching, the spatial positions of various macromolecular complexes within their native cellular context can be detected. However, the growing awareness of the reference bias introduced by the cross-correlation based approaches, and more importantly the lack of a reliable confidence measurement in the selection of these macromolecular complexes, has restricted the use of these applications. Here we propose a heuristic, in which the reference bias is measured in real space in an analogous way to the R-free value in X-ray crystallography. We measure the reference bias within the mask used to outline the area of the template, and do not modify the template itself. The heuristic works by splitting the mask into a working and a testing area in a volume ratio of 9:1. While the working area is used during the calculation of the cross-correlation function, the information from both areas is explored to calculate the M-free score. We show using artificial data, that the M-free score gives a reliable measure for the reference bias. The heuristic can be applied in template matching and in sub-tomogram averaging. We further test the applicability of the heuristic in tomograms of purified macromolecules, and tomograms of whole Mycoplasma cells.





    Categories: Journal Articles
  • Spherical deconvolution improves quality of single particle reconstruction
    [Jun 2014]

    Publication date: Available online 16 May 2014
    Source:Journal of Structural Biology

    Author(s): Gregory P. Kishchenko , Ardean Leith

    One single-particle reconstruction technique is the reconstruction of macromolecules from projection images of randomly oriented particles (SPRR). In SPRR the reliability and consequent interpretation of the final reconstruction is affected by errors arising from incorrect assignment of projection angles to individual particles. In order to improve the resolution of SPRR we studied the influence of imperfect assignment on 3D blurring. We find that this blurring can be described as a Point Spread Function (PSF) that depends on the distance from geometrical center of the reconstructed volume and that blurring is higher at the periphery. This particular PSF can be described by an almost pure tangential angular function with a negligible radial component. We have developed a reliable algorithm for spherical deconvolution of the 3D reconstruction. This spherical deconvolution operation was tested on reconstructions of GroEL and mitochondrial ribosomes. We show that spherical deconvolution improves the quality of SPRR by reducing blurring and enhancing high frequency components, particularly near the periphery of the reconstruction.





    Categories: Journal Articles
  • Crystal structure of the transport unit of the autotransporter adhesin involved in diffuse adherence from Escherichia coli
    [Jun 2014]

    Publication date: Available online 16 May 2014
    Source:Journal of Structural Biology

    Author(s): Iris Gawarzewski , Frank DiMaio , Elisa Winterer , Britta Tschapek , Sander H.J. Smits , Joachim Jose , Lutz Schmitt

    Several serious gastrointestinal diseases, which are widespread all over the world, are caused by enteropathogenic Escherichia coli. The monomeric autotransporter AIDA-I (adhesin involved in diffuse adherence) represents an important virulence factor of these strains and is involved in adhesion, biofilm formation, aggregation and invasion into host cells. Here, we present the crystal structure of the transport unit of AIDA-I at 3.0Å resolution, which forms a 12-stranded β-barrel harboring the linker domain in its pore. Mutagenesis studies of the C-terminal amino acid demonstrated the great impact of this terminal residue on membrane integration of AIDA-I and passenger translocation.





    Categories: Journal Articles
  • In silico analysis and experimental verification of OSR1 kinase – Peptide interaction
    [Jun 2014]

    Publication date: Available online 9 May 2014
    Source:Journal of Structural Biology

    Author(s): Thomas M. Austin , David P. Nannemann , Samuel L. Deluca , Jens Meiler , Eric Delpire

    The oxidative-stress-responsive kinase 1 (OSR1) and the STE20/SPS1-related proline/alanine-rich kinase (SPAK) are key enzymes in a signaling cascade regulating the activity of Na+–K+–2Cl− cotransporters (NKCC1–2) and Na+–Cl− cotransporter (NCC). Both kinases have a conserved carboxyl-terminal (CCT) domain, which recognizes a unique peptide motif present in OSR1- and SPAK-activating kinases (with-no-lysine kinase 1 (WNK1) and WNK4) as well as their substrates (NKCC1, NKCC2, and NCC). Utilizing various modalities of the Rosetta Molecular Modeling Software Suite including flexible peptide docking and protein design, we comprehensively explored the sequence space recognized by the CCT domain. Specifically, we studied single residue mutations as well as complete unbiased designs of a hexapeptide substrate. The computational study started from a crystal structure of the CCT domain of OSR1 in complex with a hexapeptide derived from WNK4. Point mutations predicted to be favorable include Arg to His or Trp substitutions at position 2 and a Phe to Tyr substitution at position 3 of the hexapeptide. In addition, de novo design yielded two peptides predicted to bind to the CCT domain: FRFQVT and TRFDVT. These results, which indicate a little bit more freedom in the composition of the peptide, were confirmed through the use of yeast two-hybrid screening.





    Categories: Journal Articles
  • Oxygen–aromatic contacts in intra-strand base pairs: Analysis of high-resolution DNA crystal structures and quantum chemical calculations
    [Jun 2014]

    Publication date: Available online 9 May 2014
    Source:Journal of Structural Biology

    Author(s): Alok Jain , R.N.V. Krishna Deepak , Ramasubbu Sankararamakrishnan

    Three-dimensional structures of biomolecules are stabilized by a large number of non-covalent interactions and some of them such as van der Waals, electrostatic and hydrogen bond interactions are well characterized. Delocalized π–electron clouds of aromatic residues are known to be involved in cation–π, CH–π, OH–π and π–π interactions. In proteins, many examples have been found in which the backbone carbonyl oxygen of one residue makes close contact with the aromatic center of aromatic residues. Quantum chemical calculations suggest that such contacts may provide stability to the protein secondary structures. In this study, we have systematically analyzed the experimentally determined high-resolution DNA crystal structures and identified 91 examples in which the aromatic center of one base is in close contact (<3.5Ǻ) with the oxygen atom of preceding (Group-I) or succeeding base (Group-II). Examples from Group-I are overwhelmingly observed and cytosine or thymine is the preferred base contributing oxygen atom in Group-I base pairs. A similar analysis of high-resolution RNA structures surprisingly did not yield many examples of oxygen–aromatic contact of similar type between bases. Ab initio quantum chemical calculations on compounds based on DNA crystal structures and model compounds show that interactions between the bases in base pairs with oxygen–aromatic contacts are energetically favorable. Decomposition of interaction energies indicates that dispersion forces are the major cause for energetically stable interaction in these base pairs. We speculate that oxygen–aromatic contacts in intra-strand base pairs in a DNA structure may have biological significance.





    Categories: Journal Articles