3D Structures of Biological Macromolecules Part 2: Nucleic Acids Jürgen Sühnel...

3D Structures of Biological Macromolecules3D Structures of Biological Macromolecules

Part 2: Nucleic AcidsPart 2: Nucleic Acids

Jürgen SühnelJürgen Sühneljsuehnel@fli-leibniz.dejsuehnel@fli-leibniz.de

Supplementary Material: www.fli-leibniz.de/www_bioc/3D/

Leibniz Institute for Age Research, Fritz Lipmann Institute,Leibniz Institute for Age Research, Fritz Lipmann Institute,Jena Centre for BioinformaticsJena Centre for Bioinformatics

Jena / GermanyJena / Germany

Molecules of LifeMolecules of Life

Nucleic AcidsNucleic Acids

DNAgenomic information (nucleosomes, chromatin)

RNAmessenger RNA, ribosomal RNA, transfer RNA, ribozymes, small RNAs, noncoding RNAs, RNAi (gene silencing),aptamers (alternatives to antibodies)

PNA peptide nucleic acids mimic nucleic acids

New Roles for RNANew Roles for RNA

Couzin J.Breakthrough of the year. Small RNAs make big splash.Science. 2002, 298, 2296-2297.

New Roles for RNANew Roles for RNA

From Gene to ProteinFrom Gene to Protein

History History

HistoryHistory

Nucleic Acid Structure Nucleic Acid Structure

NucleobasesNucleobases

/web.siumed.edu/~bbartholomew/course_material/nucleic_acids.html; no longer active)

Chain Direction in Nucleic AcidsChain Direction in Nucleic Acids

Chain Direction in Nucleic AcidsChain Direction in Nucleic Acids

Nucleic Acid BackboneNucleic Acid Backbone

Nucleic Acid Backbone Torsion AnglesNucleic Acid Backbone Torsion Angles

Ribonucleotides and DeoxyribonucleotidesRibonucleotides and Deoxyribonucleotides

Nucleic Acid Base PairsNucleic Acid Base Pairs

The ten possible purine-pyrimidine base pairs.

Source: Ignacio Tinoco, Jr. in Gesteland, R. F. and Atkins, J. F. (1993) THE RNA WORLD. Cold Spring Harbor Laboratory Press.

The seven possible homo-purinebase pairs.

Source: Ignacio Tinoco, Jr. in Gesteland, R. F. and Atkins, J. F. (1993) THE RNA WORLD. Cold Spring Harbor Laboratory Press.

Nucleic Acid Base PairsNucleic Acid Base Pairs

The four possible hetereo-purine base pairs.

Source: Ignacio Tinoco, Jr. in Gesteland, R. F. and Atkins, J. F. (1993) THE RNA WORLD. Cold Spring Harbor Laboratory Press.

Nucleic Acid Base PairsNucleic Acid Base Pairs

The seven possible pyrimidine-pyrimidine base pairs.

Nucleic Acid Base PairsNucleic Acid Base Pairs

DNA HydrationDNA Hydration

www.lsbu.ac.uk/water/nucleic.html

Nucleic Acid Base Pairs – Water-mediated PairsNucleic Acid Base Pairs – Water-mediated Pairs

Nucleic Acid Base Pairs – Water-mediated PairsNucleic Acid Base Pairs – Water-mediated Pairs

Nucleic Acid Base Pairs – Water-mediated PairsNucleic Acid Base Pairs – Water-mediated Pairs

Nucleic Acid Base Pairs with C-H…O/N InteractionsNucleic Acid Base Pairs with C-H…O/N Interactions

Nucleic Acid Base Pairs with C-H…O/N InteractionsNucleic Acid Base Pairs with C-H…O/N Interactions

Non-Canonical Base Pair DatabaseNon-Canonical Base Pair Database

http://prion.bchs.uh.edu/bp_type/

Selected Base TriplesSelected Base Triples

Base Triples in tRNABase Triples in tRNA

Base triads in the crystal structure of yeast phenylalanine transfer RNA (PDB code: 4tna).

Base Tetrads in a DNA TetraplexBase Tetrads in a DNA Tetraplex

Parallel-stranded DNA tetraplex formed from the Tetrahymena telomeric sequence d(TTGGGGT) solved by NMR spectroscopy (PDB code: 139d).The structure contains four stacked G-tetrads in the center and additional T-tetrads.

Base PolyadsBase Polyads

Base triads and a heptad in the crystal structure of a pseudoknot from beet western yellow virus (BWYV) involved in frameshifting (PDB code: 437d).The heptad is formed from two triads linked by A25.

Base PolyadsBase Polyads

HBexplore – H-bond Analysis in Proteins and Nucleic AcidsHBexplore – H-bond Analysis in Proteins and Nucleic Acids

www.imb-jena.de/www_bioc/hbx/hbx.html

Geometrical ParametersGeometrical Parametersfor Base Pairs infor Base Pairs inNucleic AcidsNucleic Acids

ndbserver.rutgers.edu/archives/report/tsukuba_sup/bp_step_hel.html

Nucleic Acid StructureNucleic Acid Structure

Nucleic Acid Structure – Sugar ConformationNucleic Acid Structure – Sugar Conformation

Nucleic Acid Structure – Sugar ConformationNucleic Acid Structure – Sugar Conformation

Nucleic Acid Structure – Sugar ConformationNucleic Acid Structure – Sugar Conformation

Nucleic Acid StructureNucleic Acid Structure

P:         P is the pitch of the helix corresponding to the distance between a base and the base obtained after walking along the DNA one full turn of 360°.

n:         n is the number on nucleotides within one pitch.h:         distance between base planes.

online-media.uni-marburg.de/chemie/bioorganic/vorlesung1/kapitel1e.html?/chemie/bioorganic/vorlesung1/k1e-20.html

DNA ConformationsDNA Conformations

www.rcsb.org/pdb/molecules/pdb23_3.html

BA Z

Ideal DNA Conformations and a Real B-DNA Structure Ideal DNA Conformations and a Real B-DNA Structure

Nucleic Acid ConformationsNucleic Acid Conformations• B-DNA is found at low salt concentrations. It is believed to be the native conformation occurring in chromatin.

In the cell nucleus DNA is complexed with about an equivalent mass of protein to form a structure known as chromatin. Chromatin is a periodic structure made up of repeating, regularly spaced subunits, the subunit being the nucleosome. Within the nucleosomes the major part of DNA is wrapped around histones. The remaining DNA joining each nucleosome is known as linker DNA.

• A-DNA In solutions with higher salt concentrations or with alcohol added A-DNA is found. • Z-DNA occurs for alternating poly(dG-dC) sequences in solutions with high salt concentrations or alcohol. • RNA occurs (contrary to DNA) almost exclusively in the A-conformation (or in a related A'-form). • There are further nucleic acid conformations like C-DNA, H-DNA or others which are not discussed

here.

Geometrical features: The distance between two subsequent base pairs along the helical axis is called helical rise (h). The pitch (p) is the length of the helix axis for one complete helix turn. The turn angle per nucleotide or twist angle (t) is given by 360° / number of nucleotides per turn. C2'-endo and C3'-endo are descriptions of sugar conformations. The most frequently occurring nucleic acid model conformations are characterized by the following geometrical parameters :• A-DNA

right-handed helix; sugar pucker: C3'-endo; number of nucleotides per pitch: 11; h: 2.56 Å; t: +32.7°. • B-DNA

right-handed helix; sugar pucker: C2'-endo; number of nucleotides per pitch: 10; h: 3.38 Å; t: +36° . • Z-DNA

left-handed helix; G: syn conformation; sugar pucker: C3'-endo; C: anti conformation, sugar pucker: C2' endo; number of nucleotides per pitch: 6x2; h: 3.7x2 Å; t= -30°x2 (for Z-DNA the repeat unit is the dimer (G-C)2.

Nucleic Acid ConformationsNucleic Acid Conformations

Groove width

Groove depth

major minor major minor

A-DNA 2.7 Å 11.0 Å 13.5 Å 2.8 Å

B-DNA 11.7 Å 5.7 Å 8.5 Å 7.5 Å

Nucleic Acid Conformations - B-DNANucleic Acid Conformations - B-DNA

Nucleic Acid Conformations - B-DNANucleic Acid Conformations - B-DNA

Nucleic Acid Conformations – B-DNANucleic Acid Conformations – B-DNA

Nucleic Acid Conformations – B-DNANucleic Acid Conformations – B-DNA

H. R. Drew, R. M. Wing, T. Takano, C. Broka, S. Tanaka, K. Itakura, R. E. Dickerson Structure Of A B-/DNA Dodecamer. Conformation And Dynamics Proc. Nat. Acad. Sci. Usa V. 78 2179 1981

First Single-crystal DNA Structure (B-DNA) First Single-crystal DNA Structure (B-DNA)

Drew-Dickerson structure

Diversity of DNA Structures Diversity of DNA Structures

Nucleosome Core Particle (1aoi)Nucleosome Core Particle (1aoi)

DNA in chromatin is organized in arrays of nucleosomes.Two copies of eachhistone protein, H2A, H2B, H3 and H4,Are assembled into an octamer that has145-147 base pairs of DNA wrappedaround it to form a nucleosome core.

Integration Host Factor (1ihf)Integration Host Factor (1ihf)

An architectural protein which assists formation of high order protein-DNA complexes such as those found in replication and long distance transcription regulation.

CURVESCURVES

www.ibpc.fr/UPR9080/Curindex.html

Integration Host Factor (1ihf) – CURVES OutputIntegration Host Factor (1ihf) – CURVES Output

Integration Host Factor (1ihf) – CURVES Output:Integration Host Factor (1ihf) – CURVES Output:Local Bending AnalysisLocal Bending Analysis

Integration Host Factor (1ihf): Local Bending Analysis Integration Host Factor (1ihf): Local Bending Analysis

Dinucleotide steps with unusual large valuesof the roll and tilt angleare indicated in red.

Integration Host Factor (1ihf): Global Bending Analysis Integration Host Factor (1ihf): Global Bending Analysis

Coordinate systemandhelical axis

Integration Host Factor (1ihf): Global Bending Analysis Integration Host Factor (1ihf): Global Bending Analysis

Coordinate systemandhelical axis

Integration Host Factor (1ihf): Global Bending AnalysisIntegration Host Factor (1ihf): Global Bending Analysis

Coordinate systemandhelical axis

Integration Host Factor (1ihf): Globale Bending Analysis Integration Host Factor (1ihf): Globale Bending Analysis

Coordinate systemandhelical axis

Integration Host Factor (1ihf): Global Bending Analysis Integration Host Factor (1ihf): Global Bending Analysis

Integration Host Factor (1ihf): Global Bending Analysis Integration Host Factor (1ihf): Global Bending Analysis

Nucleic Acid Structure - BendingNucleic Acid Structure - Bending

Cover Images for all 2003/2004/2005/2006 Issues of the Journal RNA Cover Images for all 2003/2004/2005/2006 Issues of the Journal RNA

Large Ribosomal Subunit (1jj2) - 2001Large Ribosomal Subunit (1jj2) - 2001

Jena Structures: 5S rRNA E-loop/L25 complex (1d6k)Jena Structures: 5S rRNA E-loop/L25 complex (1d6k)

IMB/FLI: Molecular Biophysics/NMR Spectroscopy (M. Görlach)

AptamersAptamers

Aptamers are DNA or RNA molecules that have been selected from random pools based on their ability to bind other molecules. Aptamers have been selected which bind nucleic acid, proteins, small organic compounds. These novel molecules have many potential uses in medicine and technology.

The Aptamer Database is a comprehensive, annotated repository for information about aptamers and in vitro selection. This resource is provided to collect, organize and distribute all the known information regarding aptamer selection.

http://aptamer.icmb.utexas.edu

AptamersAptamers

Aptamer StructuresAptamer Structures

Nf-Kappa B (P50)2 Complexed To A High-Affinity RNA Aptamer

PDB code: 1ooa

Aptamer StructuresAptamer Structures

PDB code: 1koc

RNA aptamer complex with arginine

Aptamer StructuresAptamer Structures

www.mpibpc.gwdg.de/inform/MpiNews/cientif/jahrg6/2.00/fig4.html

RNA aptamer complex with tobramycin

Aptamer StructuresAptamer Structures

PDB code: 1tob

RNA aptamer complex with tobramycin

Aptamer StructuresAptamer Structures

PDB code: 1tob

RNA aptamer complex with tobramycin

Cloverleaf Structure of tRNACloverleaf Structure of tRNA

www.mona.uwi.edu/biochem/courses/ dd120/documents/

t-RNA (4tna) - 1978

Pseudoknots

Chemical Structures of DNA and PNAChemical Structures of DNA and PNA

http://www.bentham.org/coc-sample/ganesh/ganesh.htm

RNA/PNA ComplexRNA/PNA Complex

S. C. Brown, S. A. Thomson, J. M. Veal, D. G. Davis NMR Solution Structure Of A Peptide Nucleic Acid Complexed With RNA Science V. 265 777 1994

PDB code: 176d