Summary of "Week 6 - Lecture 26"

Summary of “Week 6 - Lecture 26”

This lecture covers advanced concepts in nucleic acid structure, focusing on DNA and RNA structural varieties, base pairing interactions, and their biological significance. The discussion builds from classical DNA forms to complex folding and interactions essential for genetic function and regulation.

Main Ideas and Concepts

1. DNA Structural Forms

B-DNA: The most common DNA form, a right-handed helix characterized by:
- 10 base pairs per turn
- 3.4 Å rise per base pair
- Major and minor grooves (major groove is wider)
- Watson-Crick base pairing (A-T and G-C)
- Uniform sugar puckering (C2’-endo)
- Glycosidic torsion angle predominantly in anti conformation
Z-DNA: A left-handed helix with distinct features:
- 12 base pairs per turn
- 3.7 Å rise per base pair
- Zigzag backbone, less smooth than B-DNA
- Smaller diameter (~18 Å)
- Alternating sugar puckering (C3’-endo and C2’-endo)
- Glycosidic torsion angle alternating between syn (guanine) and anti (cytosine)
- Dimer as repeating unit (vs. monomer for B-DNA)

Structural parameters such as helix pitch, diameter, and rotation per base pair differ significantly between B-DNA and Z-DNA.

2. Glycosidic Torsion Angle (χ)

Defines rotation around the bond between the sugar and base.
Two main conformations:
- Anti: Base rotated away from the sugar; typical in B-DNA and A-DNA.
- Syn: Base rotated over the sugar; seen in Z-DNA guanine.
Important for structural modeling and NMR-based structure determination.

3. DNA Packing and Folding

DNA length (billions of base pairs) far exceeds cellular dimensions.
DNA must fold extensively, forming:
- Loops
- Bulges
- Hairpins
- Internal loops
- Multi-stem structures
RNA structures (mRNA, tRNA, rRNA) exhibit diverse folding patterns with complex base-base interactions.

4. Base Pairing Variants Beyond Watson-Crick

Standard Watson-Crick pairs: A-T (2 hydrogen bonds), G-C (3 hydrogen bonds).
Reverse Watson-Crick pairs: Bases rotated 180° around the glycosidic bond.
Hoogsteen base pairs: Alternative hydrogen bonding involving different nitrogen atoms.
Wobble base pairs: Non-standard pairs like G-U in RNA.
Other mismatches and variant pairings: A-C, G-G, A-A, C-C, U-U, C-U with various hydrogen bonding patterns.

These alternative pairings contribute to structural diversity and functional folding.

5. Higher-Order Base Interactions

Base Triples: Three bases interacting simultaneously, e.g., T-A-T and C-G-C triples.
G-quadruplexes (G-tetrads): Four guanines hydrogen-bonded in a planar, highly stable structure.
- Quadruplexes can be parallel or antiparallel with loops connecting strands.
I-motif: A structure formed by interdigitated protonated cytosine-cytosine (C-C⁺) base pairs, stabilized by protonation.

6. Functional and Biological Implications

DNA and RNA folding and structural variety are critical for:

DNA packaging in the nucleus
Regulation of gene expression
Replication and recombination processes (e.g., Holliday junctions)
Protein-DNA interactions

Transient and stable non-duplex structures play important roles in cellular function.

7. Methods of Structural Determination

NMR spectroscopy is emphasized for detecting:
- Hydrogen bond types (NH, NH₂, NHO)
- Proton-proton distances critical for defining base pairing and folding
Structural parameters like glycosidic torsion angles are key constraints in modeling.

Detailed Methodologies and Structural Features

Comparison of B-DNA and Z-DNA Parameters

Parameter B-DNA Z-DNA Base pairs per turn 10 12 Helix diameter ~20 Å ~18 Å Rise per base pair 3.4 Å 3.7 Å Helix pitch 34 Å 45 Å Rotation per base pair +36° -30°

Glycosidic Torsion Angle (χ) Definitions

Rotation around the bond between sugar C1’ and base N9 (purines) or N1 (pyrimidines).
Anti conformation: Base points away from sugar ring.
Syn conformation: Base over sugar ring, important in Z-DNA.

Base Pairing Schemes

Watson-Crick (standard)
Reverse Watson-Crick (180° rotation)
Hoogsteen and reverse Hoogsteen pairs
Wobble pairs (e.g., G-U)
Homopurine and heteropurine base pairs with various hydrogen bonding patterns
Pyrimidine-pyrimidine pairs (e.g., C-C, U-U)

Higher-Order Structures

Base triples: Third base hydrogen bonding in major groove.
Quadruplexes: Planar G-tetrads stabilized by Hoogsteen-like hydrogen bonds.
I-motif: Protonated C-C base pairs forming interdigitated duplexes.

DNA Folding Motifs

Hairpins, bulges, internal loops, symmetric and asymmetric loops.
Multi-stem loops and four-stem junctions.
Holliday junctions and other recombination intermediates.

Speakers / Sources Featured

Primary Speaker: The lecturer (unnamed) delivering Week 6 - Lecture 26.
No other speakers or external sources explicitly identified.

Summary Conclusion

This lecture provides a comprehensive overview of nucleic acid structural diversity beyond the canonical double helix, emphasizing the chemical and geometric bases of various DNA and RNA forms. It highlights the importance of alternative base pairing, folding motifs, and higher-order structures in biological function and the methodologies used to characterize these complex architectures.

The content underscores that nucleic acid structure is far more intricate than simple duplex DNA, with ongoing research needed to fully understand RNA structures and transient DNA conformations in vivo.