Download Understanding DNA Structure

Understanding DNA
Structure
I619
Structural Bioinformatics
Molecular Biology Basics + Scale
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total length of DNA in a
human cell is about 2m
DNA is compacted in length
by a factor of 10000
the compaction could be
higher (if DNA was a ball of
string)
DNA of one chromosome is
very long and narrow
(expanded scale: length =
30km, diameter = 2mm.
DNA carries genetic material
Molecular Biology Basics - Chromosomes
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Chromosomes just after duplication before cell division,
no pictures of chromosomes exist in their extended form
human DNA is stored
in 46 chromosomes
22 homologous pairs
plus X and Y
chromosomes that
determine sex
fruit fly has 8
chromosomes (3
homologous pairs + X
and Y)
Molecular Biology Basics - Chromosomes
Drosophila chromosomes
in its extended form.
Drosophila chromosomes
further magnified. A
chromosome is split into
“bands” and “interbands”
Molecular Biology Basics - Chromosomes
Scale: each DNA-protein spool is about 100Ǻ = 10–8m . Wrapping twice about each
spool reduces DNA length by about 6 times.
Molecular Biology Basics - DNA
DNA double helix. Diameter of the helix is about 20 Ǻ
Two separated strands of DNA. Each nucleotide is about 6 Ǻ wide.
Nucleotides, very basic
Each nucleotide (about 20 atoms) contains: (a) sugar, (ii) phosphate; and a (iii) base.
The phosphate group.
Nucleotides to Amino Acids
Back to Molecular Biology
Why a Helix? Let’s start from scratch!
Phosphates are very soluble in water.
Sugars are very soluble in water.
Bases are insoluble (different bases dissolve at different pH, but not pH = 7).
Ladder
A ladder formed by two strands of DNA.
Skewed Ladder
A skewed ladder formed by two strands of DNA.
Different ways of stacking
Stacking of base-pairs. Stacking of typs (b) is sterically preferred and ultimately will
be leading to helical conformation.
Helical Conformation
Base pairs wrap around an
imaginary cylinder of radius 9Ǻ.
This, using simple geometry we
can calculate that θ = 32.3˚
since P11 is directly above P0.
Typical θ in practice ranges
from 20˚ to 50˚, with the mean
of 34˚.
Helical Conformation
B DNA: 10 phosphates per turn; A DNA: 11 phosphates per turn; ZDNA: 12 phosphates per turn
What allows this flexibility?
Flexibility of the sugar-phosphate chains is considered to be the origin of flexibility.
Watson-Crick Base Pairing
Hoogsteen Base Pairing
Other Pairings?
Back to Bases (and Nucleotides)
Connecting Nucleotides
Basic DNA and
RNA Structure
• Components
•Sugar
•Base
•Phosphate
• 5’ to 3’ direction
• RNA ribose - extra
–OH at 2’ of ribose
• DNA deoxyribose
• Numbering
Voet, Donald and Judith
G. Biochemistry.
John Wiley & Sons,
1990, p. 792.
Purines
The 5 Bases
of DNA and RNA
The Nucleotides
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Pyrimadines and Purines
T->U in RNA
Names
Numbering
Bonding character
Position of hydrogen
Tautomers
Pyrimadines
Neidle, Stephen. Nucleic Acid Structure and Recognition.
Oxford University Press, 2002, p. 18.
Kinds of Double Helix
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6 degrees of freedom to move one base
pair with respect to the other
not all degrees are sterically allowed
driving force for helix formation is the
property of bases to exclude water
Base pairs typically found in “propeller
twists”
Kinds of Double Helix
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most movements are well described by
a twist, a roll and a slide.
Kinds of Double Helix
History
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1946 – DNA is the main constituent of genes
(Avery)
1950 – First X-ray pictures of DNA
(Franklin)
1953 – DNA structure revealed (Watson and
Crick)
1970 onwards - Multiple conformations and
structures
1973 X-ray structure confirms double helix
(Rich)
1974 t-RNA structure (Kim)
1980 – Structure of first complete turn of B
DNA (Dickerson)
History
http://images.google.com/imgres?imgurl=http://www.achievement.org/achievers/wat0/large/wat0-001.jpg&imgrefurl=http://www.achievement.org/autodoc/photocredit/achievers/wat0001&h=311&w=400&sz=37&tbnid=DC39azwoaZql9M:&tbnh=96&tbnw=124&prev=/images%3Fq%3Djames%2Bwatson%26um%3D1&start=1&sa=X&oi=images&ct=image&cd=1
References
• Majority of figures from “Understanding DNA” by
Calladine et al.
• Some figures from “Fundamental concepts of
Bioinformatics: by Krane and Raymer
• Some slides made by Phil Bourne, UCSD