nucleosome core particle
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The histone H3 variant CENP-A marks centromeres epigenetically and is essential for mitotic fidelity. Previous crystallographic studies of the CENP-A nucleosome core particle (NCP) reconstituted with a human α-satellite DNA derivative revealed both DNA ends to be highly flexible, a feature important for CENP-A mitotic functions. However, recent cryo-EM studies of CENP-A NCP complexes comprising primarily Widom 601 DNA reported well-ordered DNA ends. Here, we report the cryo-EM structure of the CENP-A 601 NCP determined by Volta phase-plate imaging. The data reveal that one ('left') 601 DNA end is well ordered whereas the other ('right') end is flexible and partly detached from the histone core, suggesting sequence-dependent dynamics of the DNA termini. Indeed, a molecular dynamics simulation of the CENP-A 601 NCP confirmed the distinct dynamics of the two DNA extremities. Reprocessing the image data using two-fold symmetry yielded a cryo-EM map in which both DNA ends appeared well ordered, indicating that such an artefact may inadvertently arise if NCP asymmetry is lost during image processing. These findings enhance our understanding of the dynamic features that discriminate CENP-A from H3 nucleosomes by revealing that DNA end flexibility can be fine-tuned in a sequence-dependent manner.
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.
- Publikační typ
- časopisecké články MeSH
The pyrimidine-pyrimidone (6-4) photoproduct (64-PP) is an important photoinduced DNA lesion constituting a mutational signature for melanoma. The structural impact of 64-PP on DNA complexed with histones affects the lesion mutagenicity and repair but remains poorly understood. Here we investigate the conformational dynamics of DNA-containing 64-PP within the nucleosome core particle by atomic-resolution molecular dynamics simulations and multiscale data analysis. We demonstrate that the histone core exerts important mechanical restraints that largely decrease global DNA structural fluctuations. However, the local DNA flexibility at the damaged site is enhanced due to imperfect structural adaptation to restraints imposed by the histone core. If 64-PP faces the histone core and is therefore not directly accessible by the repair protein, the complementary strand facing the solvent is deformed and exhibits higher flexibility than the corresponding strand in a naked, undamaged DNA. This may serve as an initial recognition signal for repair. Our simulations also pinpoint the structural role of proximal residues from the truncated histone tails.
The geometry of the phosphodiester backbone was analyzed for 7739 dinucleotides from 447 selected crystal structures of naked and complexed DNA. Ten torsion angles of a near-dinucleotide unit have been studied by combining Fourier averaging and clustering. Besides the known variants of the A-, B- and Z-DNA forms, we have also identified combined A + B backbone-deformed conformers, e.g. with alpha/gamma switches, and a few conformers with a syn orientation of bases occurring e.g. in G-quadruplex structures. A plethora of A- and B-like conformers show a close relationship between the A- and B-form double helices. A comparison of the populations of the conformers occurring in naked and complexed DNA has revealed a significant broadening of the DNA conformational space in the complexes, but the conformers still remain within the limits defined by the A- and B- forms. Possible sequence preferences, important for sequence-dependent recognition, have been assessed for the main A and B conformers by means of statistical goodness-of-fit tests. The structural properties of the backbone in quadruplexes, junctions and histone-core particles are discussed in further detail.
- MeSH
- A-DNA chemie MeSH
- cytosin chemie MeSH
- deoxyribonukleotidy chemie MeSH
- DNA vazebné proteiny chemie MeSH
- DNA chemie MeSH
- financování organizované MeSH
- G-kvadruplexy MeSH
- konformace nukleové kyseliny MeSH
- křížová struktura DNA chemie MeSH
- ligandy MeSH
- nukleozomy chemie MeSH
- RNA chemie MeSH
- sekvence nukleotidů MeSH
... Are a Basic Unit of Eukaryotic Chromosome Structure -- The Structure of the Nucleosome Core Particle ... ... Reveals How DNA Is Packaged -- Nucleosomes Have a Dynamic Structure, and Are Frequently Subjected to ... ... Changes Catalyzed by ATP-Dependent Chromatin Remodeling Complexes Nucleosomes Are Usually Packed Together ... ... Affinity and Specificity for DNA 375 -- Transcription Regulators Bind Cooperatively to DNA 378 -- Nucleosome ... ... Tissue Morphogenesis and Repair -- Proteoglycans Are Composed of GAG Chains Covalently Linked to a Core ...
Sixth edition xxxiv, 1430 stran v různém stránkování : ilustrace (převážně barevné) ; 29 cm
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- molekulární biologie, molekulární medicína
- NLK Publikační typ
- učebnice vysokých škol
... Macromolecules Can Penetrate Cell Membranes Directly 311 -- Specialized Phagocytic Cells Ingest Particles ... ... , the Unit Particles of Chromatin -- Nucleosomes Are Packed Together to Form Regular Higher-Order Structures ... ... -- Histone HI Proteins Help Pack Nucleosomes Together Not All Nucleosomes Are Packed in Precisely the ... ... -- New RNA Is Packaged in Ribonucleoprotein Particles The Precursors of Messenger RNA Are Covalently ... ... - Summary 561 -- Ciliary Movement 561 -- Cilia and Flagella Propagate Bending Movements 561 -- The Core ...
xxxix, 1146 s. : il., tab. ; 28 cm
- MeSH
- biologie buňky MeSH
- molekulární biologie MeSH
- Publikační typ
- monografie MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biologie
- cytologie, klinická cytologie
... 60 -- 3.4 Tertiary Structure: Water-Soluble Proteins -- Fold into Compact Structures with Nonpolar Cores ... ... Cognate DNA Molecules, Ensuring Specificity 248 -- 9.3.4 Type II Restriction Enzymes Have a Catalytic -- Core ... ... 19.2.1 Photosynthetic Bacteria and the Photosynthetic Reaction Centers of Green Plants Have a Common Core ... ... Complexity of Eukaryotic -- Genomes Requires Elaborate Mechanisms for Gene Regulation 874 -- 31.2.1 Nucleosomes ... ... Complexes of DNA and -- Histones 875 -- 31.2.2 Eukaryotic DNA Is Wrapped Around Histones to Form Nucleosomes ...
5th ed. xvii, 974 s. : il., tab., grafy ; 32 cm
