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Nucleic Acid Structure
Many thanks to Dave Bevan for providing
some of the material for this lecture.
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The Central Dogma
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Nucleic Acids are Linear Polymers
Berg, J.M. et al. (2002) Biochemistry, Fifth Edition, W.H. Freeman and Co.
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Structure of nucleotides
A phosphate group
Nucleotides have three characteristic components:
A nitrogenous base(pyrimidines or purine)
A pentose sugar
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The phosphate
Carries a negative electric charge!
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The Sugars of Nucleic Acids
Berg, J.M. et al. (2002) Biochemistry, Fifth Edition, W.H. Freeman and Co.
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Berg, J.M. et al. (2002) Biochemistry, Fifth Edition, W.H. Freeman and Co.
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The Bases of Nucleic Acids
Berg, J.M. et al. (2002) Biochemistry, Fifth Edition, W.H. Freeman and Co.
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Backbones of DNA and RNA
Berg, J.M. et al. (2002) Biochemistry, Fifth Edition, W.H. Freeman and Co.
h d b l d
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The major deoxyribonucleotides
N l i id
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Nucleic acids
Nucleotide monomerscan be linked together via aphosphodiester linkage
formed between the 3' -OHof a nucleotideand the phosphate of thenext nucleotide.
Two ends of the resulting poly-or oligonucleotide are defined:
The 5' end lacks a nucleotide atthe 5' position,
and the 3' end lacks a nucleotide
at the 3' end position.
C l l d d l d
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Compare polynucleotides and polypeptides
• As in proteins, the sequence of side chains(bases in nucleic acids) plays an important
role in function.• Nucleic acid structure depends on thesequence of bases and on the type of ribose
sugar (ribose, or 2'-deoxyribose).• Hydrogen bonding interactions areespecially important in nucleic acids.
Expectedly, weak bonds.
I d H b di b DNA b
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Interstrand H-bonding between DNA bases
Watson-Crick base pairing
DNA t t d t i ti
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DNA structure determination
• Franklin collected x-raydiffraction data (early 1950s)that indicated 2 periodicitiesfor DNA: 3.4 Å and 34 Å.
• Watson and Crick proposed a 3D
model accounting for the data.
DNA t t
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DNA structure
• DNA consists of two helicalchains wound around thesame axis in a right-handedfashion aligned in an
antiparallel fashion.• There are 10.5 base pairs, or
36 Å, per turn of the helix.
• Alternating deoxyribose andphosphate groups on thebackbone form the outsideof the helix.
• The planar purine andpyrimidine bases of bothstrands are stacked insidethe helix.
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Watson-Crick Base Pairing
Berg, J.M. et al. (2002) Biochemistry, Fifth Edition, W.H. Freeman and Co.
DNA str nds
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DNA strands
• The antiparallel strands of DNA arenot identical, but are complementary.
• This means that they are positioned
to align complementary base pairs: Cwith G, and A with T.• So you can predict the sequence of
one strand given the sequence of its
complement.• Useful for information storage and
transfer!
• Note sequence conventionally is givenfrom the 5' to 3' end
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DNA Double HelixBackbones in darker blue and red.
Bases in lighter blue and pink.
Berg, J.M. et al. (2002) Biochemistry, Fifth Edition, W.H. Freeman and Co.
20 A
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Forms of DNAMost prevalent
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DNA Backbone Parameters
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DNA Grooves
Berg, J.M. et al. (2002) Biochemistry, Fifth Edition, W.H. Freeman and Co.
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DNA Packing
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The DNA is flexible. It is important to
understand how it bends.Why is this important? Here is the one reason that is often cited:
12 feet
So the DNA in the cell must be really bent.
One reason (out of many) why it is important to
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( y) y pknow how the DNA is folded up in the cell.
The DNA in all your cells is identical. Yet cellsare different. For instance, the DNA in the eye
cells is exactly the same as in the tongue cells.
But it is packed differently, exposing differentparts for reading by the cell when it develops
and functions. Roughly speaking, that is whatmakes cells of the same organism different
from each other.
Obviously, the folding will depend
on how flexible the DNA is.
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Tightly bent DNA is a fact of life:
~ 80 A
~25 bp
~500A
~ 145 bp~100A
~30 bp
DNA loopingmediated by a
transcription factor
DNA packingin the nucleosome DNA packing
inside a virus
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Weakly and Tightly bent DNA.
Persistence length.
Weak bending. Energy > kT
The key length scale of a polymer: persistence length.
Conventional value = ~145 pb or ~500A for DNA
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Classical elastic rod theory (Landau)
φ
2φ ∝Bending energy
Hooke’s Law Harmonic WLC model.
2
0
)( φ kT dss
t kTL E
C
≥∂
∂≈ ∫
(In our case, L = C ~ 500A. )
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DNA flexibility depends on its sequence!
• It is very important to be able to predict
this dependence (still not fully solved
problem).• What’s more flexible: AAAAA
TTTTTTOr: GGGGGG
CCCCCC
A-T linked by 2 H-bonds, but G-C by 3.
Less room to wiggle, so less flexible.
Ribose
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Ribose
• An important derivative ofribose is 2'-deoxyribose,or just deoxyribose, inwhich the 2' OH is
replaced with H.• Deoxyribose is in DNA(deoxyribonucleic acid)
• Ribose is in RNA(ribonucleic acid).
• The sugar prefersdifferent puckers in DNA
(C-2' endo) and RNA C-3'endo).
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Types of RNA
• mRNA (messenger RNA)
– Template for protein synthesis (translation)
• tRNA (transfer RNA)
– Carries activated amino acids to ribosome forprotein synthesis
– At least one kind of tRNA for each of the 20 amino
acids• rRNA (ribosomal RNA)
– Major component of ribosomes
RNA has a rich and varied structure
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RNA has a rich and varied structure
Watson-Crick base pairs(helical segments;Usually A-form).
Helix is secondarystructure.Note A-U pairs inRNA.
DNA canform
structureslike this aswell.
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Structure of tRNA
RNA displays interesting tertiary structure
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p y g y
Single-strandedRNA
right-handedhelix
T. thermophila intron,A ribozyme (RNA enzyme)(1GRZ)
Hammerhead ribozyme
(1MME)
Yeast tRNAPhe(1TRA)
The mother of all proteins
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he mother of a prote ns
1ffk
Large subunit of the ribosomeMade of proteins and RNA.
Function: protein sysnthesis
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