Nejvíce citovaný článek - PubMed ID 27150812
DNATCO: assignment of DNA conformers at dnatco.org
The revolution in cryo-electron microscopy has resulted in unprecedented power to resolve large macromolecular complexes including viruses. Many methods exist to explain density corresponding to proteins and thus entire protein capsids have been solved at the all-atom level. However methods for nucleic acids lag behind, and no all-atom viral double-stranded DNA genomes have been published at all. We here present a method which exploits the spiral winding patterns of DNA in icosahedral capsids. The method quickly generates shells of DNA wound in user-specified, idealized spherical or cylindrical spirals. For transition regions, the method allows guided semiflexible fitting. For the kuravirus SU10, our method explains most of the density in a semiautomated fashion. The results suggest rules for DNA turns in the end caps under which two discrete parameters determine the capsid inner diameter. We suggest that other kuraviruses viruses may follow the same winding scheme, producing a discrete rather than continuous spectrum of capsid inner diameters. Our software may be used to explain the published density maps of other double-stranded DNA viruses and uncover their genome packaging principles.
Water plays an important role in stabilizing the structure of DNA and mediating its interactions. Here, the hydration of DNA was analyzed in terms of dinucleotide fragments from an ensemble of 2727 nonredundant DNA chains containing 41 853 dinucleotides and 316 265 associated first-shell water molecules. The dinucleotides were classified into categories based on their 16 sequences and the previously determined structural classes known as nucleotide conformers (NtCs). The construction of hydrated dinucleotide building blocks allowed dinucleotide hydration to be calculated as the probability of water density distributions. Peaks in the water densities, known as hydration sites (HSs), uncovered the interplay between base and sugar-phosphate hydration in the context of sequence and structure. To demonstrate the predictive power of hydrated DNA building blocks, they were then used to predict hydration in an independent set of crystal and NMR structures. In ten tested crystal structures, the positions of predicted HSs and experimental waters were in good agreement (more than 40% were within 0.5 Å) and correctly reproduced the known features of DNA hydration, for example the `spine of hydration' in B-DNA. Therefore, it is proposed that hydrated building blocks can be used to predict DNA hydration in structures solved by NMR and cryo-EM, thus providing a guide to the interpretation of experimental data and computer models. The data for the hydrated building blocks and the predictions are available for browsing and visualization at the website https://watlas.datmos.org/watna/.
- Klíčová slova
- DNA hydration, WatNA, dinucleotide fragments, knowledge-based prediction, water,
- MeSH
- DNA * chemie MeSH
- konformace nukleové kyseliny MeSH
- nukleotidy MeSH
- voda * chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA * MeSH
- nukleotidy MeSH
- voda * MeSH
Solution and crystal data are reported for DNA 18-mers with sequences related to those of bacterial noncoding single-stranded DNA segments called repetitive extragenic palindromes (REPs). Solution CD and melting data showed that the CG-rich, near-palindromic REPs from various bacterial species exhibit dynamic temperature-dependent and concentration-dependent equilibria, including architectures compatible with not only hairpins, which are expected to be biologically relevant, but also antiparallel duplexes and bimolecular tetraplexes. Three 18-mer oligonucleotides named Hpar-18 (PDB entry 6rou), Chom-18 (PDB entry 6ros) and its brominated variant Chom-18Br (PDB entry 6ror) crystallized as isomorphic right-handed A-like duplexes. The low-resolution crystal structures were solved with the help of experimental phases for Chom-18Br. The center of the duplexes is formed by two successive T-T noncanonical base pairs (mismatches). They do not deform the double-helical geometry. The presence of T-T mismatches prompted an analysis of the geometries of these and other noncanonical pairs in other DNA crystals in terms of their fit to the experimental electron densities (RSCC) and their geometric fit to the NtC (dinucleotide conformational) classes (https://dnatco.datmos.org/). Throughout this work, knowledge of the NtC classes was used to refine and validate the crystal structures, and to analyze the mismatches.
- Klíčová slova
- CD spectra, DNA structure, REPs, T–T mismatch, crystal structure, noncanonical base pairs, repetitive extragenic palindromes,
- MeSH
- Cardiobacterium genetika MeSH
- DNA bakterií chemie MeSH
- Haemophilus parasuis genetika MeSH
- molekulární modely MeSH
- molekulární struktura * MeSH
- nukleotidové motivy * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA bakterií MeSH
A detailed description of the dnatco.datmos.org web server implementing the universal structural alphabet of nucleic acids is presented. It is capable of processing any mmCIF- or PDB-formatted files containing DNA or RNA molecules; these can either be uploaded by the user or supplied as the wwPDB or PDB-REDO structural database access code. The web server performs an assignment of the nucleic acid conformations and presents the results for the intuitive annotation, validation, modeling and refinement of nucleic acids.
- Klíčová slova
- annotation, nucleic acids, refinement, structural alphabets, validation,
- MeSH
- databáze nukleových kyselin MeSH
- DNA chemie MeSH
- internet MeSH
- konformace nukleové kyseliny MeSH
- molekulární modely MeSH
- RNA chemie MeSH
- software * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA MeSH
- RNA MeSH
By analyzing almost 120 000 dinucleotides in over 2000 nonredundant nucleic acid crystal structures, we define 96+1 diNucleotide Conformers, NtCs, which describe the geometry of RNA and DNA dinucleotides. NtC classes are grouped into 15 codes of the structural alphabet CANA (Conformational Alphabet of Nucleic Acids) to simplify symbolic annotation of the prominent structural features of NAs and their intuitive graphical display. The search for nontrivial patterns of NtCs resulted in the identification of several types of RNA loops, some of them observed for the first time. Over 30% of the nearly six million dinucleotides in the PDB cannot be assigned to any NtC class but we demonstrate that up to a half of them can be re-refined with the help of proper refinement targets. A statistical analysis of the preferences of NtCs and CANA codes for the 16 dinucleotide sequences showed that neither the NtC class AA00, which forms the scaffold of RNA structures, nor BB00, the DNA most populated class, are sequence neutral but their distributions are significantly biased. The reported automated assignment of the NtC classes and CANA codes available at dnatco.org provides a powerful tool for unbiased analysis of nucleic acid structures by structural and molecular biologists.
- MeSH
- biokatalýza MeSH
- DNA chemie klasifikace MeSH
- konformace nukleové kyseliny * MeSH
- nukleotidové motivy * MeSH
- nukleotidy chemie klasifikace MeSH
- reprodukovatelnost výsledků MeSH
- riboswitch MeSH
- ribozomy chemie metabolismus MeSH
- RNA katalytická chemie metabolismus MeSH
- RNA chemie klasifikace MeSH
- vazebná místa MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA MeSH
- nukleotidy MeSH
- riboswitch MeSH
- RNA katalytická MeSH
- RNA MeSH
Structural bioinformatics provides the scientific methods and tools to analyse, archive, validate, and present the biomolecular structure data generated by the structural biology community. It also provides an important link with the genomics community, as structural bioinformaticians also use the extensive sequence data to predict protein structures and their functional sites. A very broad and active community of structural bioinformaticians exists across Europe, and 3D-Bioinfo will establish formal platforms to address their needs and better integrate their activities and initiatives. Our mission will be to strengthen the ties with the structural biology research communities in Europe covering life sciences, as well as chemistry and physics and to bridge the gap between these researchers in order to fully realize the potential of structural bioinformatics. Our Community will also undertake dedicated educational, training and outreach efforts to facilitate this, bringing new insights and thus facilitating the development of much needed innovative applications e.g. for human health, drug and protein design. Our combined efforts will be of critical importance to keep the European research efforts competitive in this respect. Here we highlight the major European contributions to the field of structural bioinformatics, the most pressing challenges remaining and how Europe-wide interactions, enabled by ELIXIR and its platforms, will help in addressing these challenges and in coordinating structural bioinformatics resources across Europe. In particular, we present recent activities and future plans to consolidate an ELIXIR 3D-Bioinfo Community in structural bioinformatics and propose means to develop better links across the community. These include building new consortia, organising workshops to establish data standards and seeking community agreement on benchmark data sets and strategies. We also highlight existing and planned collaborations with other ELIXIR Communities and other European infrastructures, such as the structural biology community supported by Instruct-ERIC, with whom we have synergies and overlapping common interests.
- Klíčová slova
- ELIXIR, Instruct-ERIC, biomolecular structure, nucleic acids structure, protein structure, structural bioinformatics,
- MeSH
- biologické vědy * MeSH
- genomika MeSH
- lidé MeSH
- proteiny MeSH
- výpočetní biologie organizace a řízení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
- Názvy látek
- proteiny MeSH
DNA is a structurally plastic molecule, and its biological function is enabled by adaptation to its binding partners. To identify the DNA structural polymorphisms that are possible in such adaptations, the dinucleotide structures of 60 000 DNA steps from sequentially nonredundant crystal structures were classified and an automated protocol assigning 44 distinct structural (conformational) classes called NtC (for Nucleotide Conformers) was developed. To further facilitate understanding of the DNA structure, the NtC were assembled into the DNA structural alphabet CANA (Conformational Alphabet of Nucleic Acids) and the projection of CANA onto the graphical representation of the molecular structure was proposed. The NtC classification was used to define a validation score called confal, which quantifies the conformity between an analyzed structure and the geometries of NtC. NtC and CANA assignment were applied to analyze the structural properties of typical DNA structures such as Dickerson-Drew dodecamers, guanine quadruplexes and structural models based on fibre diffraction. NtC, CANA and confal assignment, which is accessible at the website https://dnatco.org, allows the quantitative assessment and validation of DNA structures and their subsequent analysis by means of pseudo-sequence alignment. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:Acta_Cryst_D:2.
- Klíčová slova
- DNA modelling, DNA structure, NMR structure, X-ray structure, bioinformatics,
- MeSH
- DNA chemie MeSH
- konformace nukleové kyseliny * MeSH
- molekulární modely * MeSH
- počítačová grafika MeSH
- simulace molekulární dynamiky MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA MeSH
We analyzed the structural behavior of DNA complexed with regulatory proteins and the nucleosome core particle (NCP). The three-dimensional structures of almost 25 thousand dinucleotide steps from more than 500 sequentially non-redundant crystal structures were classified by using DNA structural alphabet CANA (Conformational Alphabet of Nucleic Acids) and associations between ten CANA letters and sixteen dinucleotide sequences were investigated. The associations showed features discriminating between specific and non-specific binding of DNA to proteins. Important is the specific role of two DNA structural forms, A-DNA, and BII-DNA, represented by the CANA letters AAA and BB2: AAA structures are avoided in non-specific NCP complexes, where the wrapping of the DNA duplex is explained by the periodic occurrence of BB2 every 10.3 steps. In both regulatory and NCP complexes, the extent of bending of the DNA local helical axis does not influence proportional representation of the CANA alphabet letters, namely the relative incidences of AAA and BB2 remain constant in bent and straight duplexes.
- Klíčová slova
- DNA, DNA-protein recognition, histone, molecular structure, nucleosome core particle, regulatory proteins, transcription factors,
- Publikační typ
- časopisecké články MeSH
