An
Introduction to
DNA Structure
David Marcey
© 2006
I.
The DNA Polymer
II. The B-DNA Double Helix
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I.
The DNA Polymer
In the left frame
is a short stretch of a single strand of DNA. DNA is a polymer of
linked deoxyribonucleotides. Here the atoms are colored according
to the standard CPK coloring scheme (C,
N,
O,
P).
For simplicity, hydrogen atoms are not shown.
In the tetrameric example shown, each of the four deoxyribonucleotide
building blocks (dA, dT,
dC, dG)
is represented.
As shown here for dC, each deoxyribonucleotide
in the chain comprises a nitrogenous base,
a deoxyribose sugar, and a phosphate
group (phosphorus plus oxygens).
The carbons of the sugar are numbered 1'-5' as indicated.
The nitrogenous base is linked to the
sugar by a glycosidic bond between a nitrogen
and the 1' carbon of the deoxyribose sugar.
The 5' carbon of
each sugar is linked to a phosphorus
through an oxygen
(ester bond). The phosphorus
is in turn linked to the 3'
oxygen of the next
nucleotide in the chain.
The connection between nucleotides in
a DNA strand is thus referred to as a phosphodiester
linkage.
The molecule can be viewed as a series of nitrogenous
bases (CPK coloration) connected through a sugar-phosphate
backbone.
For
study (using CPK coloration):
- identify
the four
nitrogenous bases
- identify
the 5' and 3' carbons of the ribose sugars
- identify
the phosphodiester
linkages connecting the nucleotides
- moving
top to bottom, how would you label the polarity of the sugar-phosphate
backbone, 3' ---> 5' or 5' --->3' ? Why?
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II. The B-DNA
Double Helix
DNA
in the cell functions as a double-stranded helix of B-form DNA, the
structure of which was first determined by Watson and Crick. Here
the two strands are differentially colored to illustrate the right
handed B-form helix clearly.
The polar sugar-phosphate backbones
of each strand form the helical scaffold, with the nitrogenous bases
in the interior of the molecule, their planes nearly perpendicular
to the helical axis. Each base forms hydrogen bonds (indicated by
dashed lines) with a base from the opposite strand.
The polarity of the backbones
is antiparallel, with one strand running 3' ---> 5' and
the other 5' --->3'. This can readily be seen by observing
the reversed orientations of the ribose sugars on opposite strands.
The diameter of the B-DNA
is ~20 Angstroms, and the distance between base
pairs is ~3.4 Angstroms.
The base pairing of opposite strands is stereochemically
selective, Adenine always pairing with
Thymine, and Guanine
with Cytosine.
Two and three hydrogen
bonds are formed in A-T and G-C base pairs, respectively.
A-T
and G-C
base pairing results in strand complementarity, with one strand of
the double helix forming a sequence of bases complementary in hydrogen
bonding to that of the other strand. As noted by Watson and Crick
in their 1953 paper describing the first model of the DNA double helix,
base complementarity provides a means by which the genetic material
can replicate with fidelity. Each strand of a parent double helix
serves as a template upon which complementary strands are built, producing
two daughter molecules identical to the parent, with one strand of
each daughter helix conserved from the parent molecule.
This semi-conservative mode of replication is
here illustrated schematically for 1 strand of DNA.
The attachment of bases to the backbone sugars
through glycosidic bonds is asymmetrical. This results in the formation
of two different grooves on opposite sides of the base pairs, the
major and minor grooves. Although the grooves are of similar depth
in B-DNA, the major groove is considerably wider than the minor groove,
the distance between the sugar-phosphate backbones being much greater
in the former.
The edges of the base pairs present a more complex
sterochemical environment in the major groove than in the minor groove.
As can be observed in the T-A base pair shown, the major groove edge
contains a methyl group (CH3), a hydrogen bond acceptor (HA), a hydrogen
bond donor (HD), and a second hydrogen bond acceptor (HA) [for simplicity,
hydrogens are not shown]. The minor groove edge, in contrast, presents
only a HA, a hydrogen (H), and a second HA. Whereas a switch to an
A-T base pair would present a reversed edge chemistry in the major
groove (HA-HD-HA-CH3), the edge in the minor groove (HA-H-HA) would remain essentially the
same as in a T-A pair (HA-H-HA). Similar considerations apply to C-G
and G-C base pairs. Since many proteins that bind DNA recognize specific
sequences of bases, it is not surprising that most bind to the floor
of the major groove, as this provides more chemical information for
recognition than the minor groove.
The major
and minor grooves lie 180o
opposite each other in the double helix, spiraling along the axis
of the molecule.
A view of DNA's molecular surface clearly illustrates the similar
depth and different widths of the major and minor grooves.
The B-DNA helix
is one of three major conformations for double helical DNA. The other
conformers are A- and Z-DNA. For a brief discussion of DNA conformers,
see the DNA
Conformers exhibit.
For study:
- identify
the base
paired nitrogenous bases
- identify
the atoms involved in hydrogen bonding between base pairs
- identify
the hydrogen
donor and acceptor atoms for each hydrogen bond
- for
both A-T and G-C base pairs, identify the edges of the bases
that
form the floors of the major and minor grooves
- for
both A-T and G-C base pairs, identify the groups on the floors
of
the grooves that could serve as recognition sites for interacting
molecules
- for
each base pair, explain why the major groove is richer in
chemical information than the minor groove
For
study:
- identify
the major
and minor grooves in double helical DNA
- compare
the depth and width of the grooves, and note the distance
between backbones in each groove
- imagine
that you are a protein that must recognize a particular sequence
of base pairs in double helical DNA - list the reasons why
you most likely will bind DNA in the major groove
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