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(Unit II) Chapter 6: The Structure of

DNA

Introduc;on to DNA Structure: The

Importance of DNA Structure

DNA, since it carries all the informa;on for a

given organism, must be a molecule that
contains an incredible amount of
informa;on

Contains informa;on for proper

development of an organism

Contains the informa;on for proper cellular

func;on

Allows the proper structures to form at the

appropriate ;me
Allows appropriate growth at the
appropriate ;me

DNA encodes the informa;on to produce

proteins involved in respira;on
DNA encodes the informa;on to produce
proteins that are important in sending and
receiving signals between cells

All the appropriate informa;on is also

passed on to subsequent genera;ons

Cellular reproduc;on (asexual)

Organismal reproduc;on (sexual or asexual)

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Introduc;on to DNA Structure: How It

Holds The Informa;on of Heredity

The ability of DNA to hold all of this

informa;on lies in both its chemistry and 3-
Dimensional structure

DNA contains only ve dierent types of

atoms

When Watson and Crick (1952) discovered

that the 3-Dimensional structure of DNA

Carbon
Phosphorous
Nitrogen
Hydrogen
Oxygen

Found that the molecule takes the shape

double helix
More importantly understood how the
dierent atoms found in DNA are covalently
linked together and how these linkages are
viewed in 3-dimensions

Watson and Crick saw that DNA was a

polymer made of repea;ng building blocks
known as nucleo;des

Building the DNA Molecule: The Chemical

Structure of Deoxyribonucleic Acid

Each nucleo;de consists of three

basic components
Phosphate group
A ve carbon sugar (deoxyribose)
A nitrogenous base

The phosphate group and the

deoxyribose are part of the DNA
backbone, whereas the nitrogenous
bases are located towards the
interior of the DNA molecule

More specically, it is the sequence

and number of these nitrogenous
bases (which are part of nucleo;des)
that give each gene its own iden;ty
Genes dier in the number of bases
Genes dier in the sequence of bases

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Building the DNA Molecule: Nucleo;de

Structure and The Pentose Sugars
To start, each nucleo;de will
contain a central pentose (5
carbon) sugar
The sugar that is used in DNA is
deoxyribose
Within the ring, there are four
carbon atoms (labeled 1, 2, 3
etc) joined by an oxygen atom
The [h carbon (the 5 carbon)
projects upward from the ring
To build the nucleo;de, we are
going to a\ach other chemically
reac;ve groups to specic
carbons in the pentose sugar

Building the DNA Molecule: The

Nitrogenous Base Component
The presence of the nitrogenous
bases in nucleic acids was
discovered by Friedrich Miecher
a[er he started to determine the
chemistry of his nuclein
They are called nitrogenous
bases due to the fact that they
are have a high nitrogen content
They are considered a base due
to the fact that they have the
proper;es of a base (proton
acceptors)
By and large, the structure of
DNA the nitrogenous bases are
non-polar, which is important for
DNA structure
The bases are hydrophobic
The bases are located towards the
interior of a molecule of DNA

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Building the DNA Molecule: The

Nitrogenous Base Component

There are four common nitrogenous

bases found in DNA

Adenine
Guanine
Cytosine
Thymine

Adenine and Guanine are known as

purines and have a double ring

Cytosine, Thymine are known as

pyrimidines and have a single ring

Building the DNA Molecule: The

Nitrogenous Base Component

In nature, each nitrogenous base can take one of

two conforma;ons

For the nitrogenous bases, there are two

conforma;ons

Deni;on of Tautomers:

Tautomers are isomers that readily interconvert at

equilibrium
Tautomeriza;on results in the migra;on of a proton
and a resul;ng shi[ from single to double bond, or
vice versa

The two states in equilibrium with each other

Conven;onal form
Tautomeric state

Conven;onal
Tautomeric

For all of the nitrogenous bases, the equilibrium

strongly favors the conven;onal form

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Building the DNA Molecule: Nucleo;de

Structure and The Phosphate Group

The chemistry of the phosphate group

is important in allowing DNA to be a
polymer (i.e. the phosphate group is
important in linking nucleo;des
together)

The phosphate group consists of a

phosphorus and four oxygen atoms

The phosphorous is located centrally in

the phosphate group, and each of the
four oxygen atoms are bound to the
phosphorous

The bonds between the phosphorous

and each oxygen atom is unequal
They share electrons unequally
Oxygen atoms are slightly nega;ve
Phosphate is slightly posi;ve

Building the DNA Molecule: Nucleo;de

Structure and The Phosphate Group

At physiological pH, the phosphate group is

a proton donor

Phosphate group is polar

Phosphate group has a slight nega;ve charge

Ester bonds link the phosphate to the rest of

the nucleo;de

They have the property of being extremely

stable
These bonds are easily broken by enzyma;c
hydrolysis (by adding water)

The chemistry of the phosphate group also

allows for linking of nucleo;des together

Phosphate bonds are stable, yet easily

broken

Allows for polymeriza;on of nucleo;des

Allows for synthesis of DNA (or RNA) chains

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Building the DNA Molecule: Construc;ng a

Nucleo;de-The Basic Building Block of DNA

To build a nucleo;de one must start with a

nucleoside

A nucleoside consists of only a pentose

sugar and a nitrogenous base

The nitrogenous base is bound to the 1

carbon through an N-glycosidic linkage,
which is formed through a condensa;on
reac;on

There are proper naming conven;ons for

each type of nucleoside

Deoxyguanosine (if containing guanine and

dexoyribose)
Deoxycy;dine (if containing cytosine and
deoxyribose)
Deoxyadenosine (if containing adenine and
deoxyribose)
Deoxythymidine (if containing thymine and
deoxyribose)

Building the DNA Molecule: Construc;ng a

Nucleo;de-The Basic Building Block of DNA

In a nucleo;de the phosphate group

is bound to the 5 carbon

Like the nitrogenous base and the

phosphate group are added to the
pentose via condensa;on reac;ons
with water as the byproduct

A nucleo;de can have one, two or

three phosphates bound to the 5
carbon

The phosphate that is bound to the 5

carbon is known as the phosphate
The second phosphate from the 5
carbon is the phosphate
The third phosphate from the 5 carbon
is the phosphate

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Building the DNA Molecule: Naming

the Nucleo;des
The name of a nucleo;de comes
uses as a root the name of the
nucleoside followed by the
number of phosphates the
nucleo;de contains

A nucleo;de containing
deoxyribose, adenosine and one
phosphate is deoxyadenosine
monophosphate
A nucleo;de containing
deoxyribose guanosine and two
phosphates is deoxyguanosine
diphosphate
A nucleo;de containing
deoxyribose, thymidine and three
phosphates is deoxythymidine
triphosphates

Building a DNA Molecule: A Strand of DNA Is

Composed of Chains of Polynucleo;des

A single polymer of DNA is considered a strand,

with each strand having specic polarity (the two
ends have dierent free func;onal groups)

To create a DNA strand, a polymer must be formed

of repea;ng nucleo;des

A strand of DNA is only formed in the 5 3

direc;on and never in the 3 5 direc;on

In forming a strand of DNA, the nucleo;des will

only be added onto the 3 end of a growing DNA
strand

In order to join two nucleo;des together, a

condensa;on reac;on must occur between the
free 3OH group of the nal nucleo;de in a growing
strand and the 5 PO4 group in the nucleo;de to be
added

A phosphodiester bond is formed between the two

nucleo;des
A byproduct of the reac;on is one molecule of water

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Building the DNA Molecule: DNA Base

Pairing

DNA is a double stranded molecule and therefore,

two strands must be able to interact with each
other

The results of two very important experiments

were important for showing how the two strands
of a DNA molecule interact

Erwin Chargas biochemical experiments (rst)

Watson and Cricks X-ray dirac;on studies (second)

Charga wanted to determine the rela;ve

concentra;on of each nitrogenous base within a
molecule of DNA

In 1940, Charga developed a paper

chromatography method to analyze the amount of
each nitrogenous base present in a molecule of
DNA

Charga observed several important rela;onships

among the molar concentra;ons of the dierent
bases

In 1940 Charga proposed three important rules

with regards to the nitrogenous base composi;on
of DNA, which became known as Chargas rules

Building the DNA Molecule: DNA Base

Pairing

Charga rules are as follows

[A] = [T]
[G] = [C]
[A] + [G] = [T] + [C] or the
concentra;on of purines is equal to the
concentra;on of pyrimidines

Charga also found that the base

composi;on, as dened by the
percentage of G and C (G+C content)
for DNA is the basically the same for
organisms of the same species, and
dierent for organisms of dierent
species

The G + C content can vary from 22

73% depending on the organism

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Building the DNA Molecule: DNA Base

Pairing

Watson and Crick built o Chargas

work

Watson and Crick isolated and

crystallized DNA then subjected it to
X-ray dirac;on analysis to
determine the structure of the DNA

Their results show that the

secondary structure of DNA was a
double helix

In the double helix, the two DNA

strands interacted through base
pairing (showing a physical reason
for Chargas observa;ons
Adenine pairs with thymine (2 H
bonds)
Guanine pairs with cytosine (3 H
bonds)

Building the DNA Molecule: DNA Base

Pairing

The two strands in a DNA molecule

lie in an an;parallel congura;on
Opposite orienta;on = an;-parallel
Allows the nitrogenous bases to align
properly for ecient base pairing
The free 5 ends of each strand are on
opposite sides of the molecule
The free 3 ends of each strand are also
on opposite sides from each other

Base pairing is advantageous to the

DNA chemistry
Excludes water from the interior of the
DNA molecule
Creates entropy which allows for
stabiliza;on of the double helix

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Building the DNA Molecule: DNA Base

Pairing

Each strand of a DNA molecule has

complementary sequence

There are important conven;ons that need

to be followed when wri;ng the sequence
of a DNA strand

Due base pairing between the two strands

Where there is an Adenine in one strand,
there will be a Thymine opposite etc.
The two strands do not have the same
sequence

The sequence of each strand is wri\en

separately
Only the sequence of the nitrogenous bases
is wri\en out
The sequence of each strand is ALWAYS
wri\en in the 5 3 direc;on
A 5 is wri\en before the 5 most nitrogenous
base and a 3 is wri\en a[er the 3 most
nitrogenous base

For the DNA molecule on the right the

sequence of the two strands are as follows

For the strand 5 3 bo\om to top (le[

strand) the sequence is 5 CAGT 3
For the strand 5 3 top to bo\om (right
strand) the sequence is 5 ACTG 3

DNA Secondary Structure: The Structure Confers Stability

and Allows The Molecule To Hold Vast Amounts of
Informa;on

If DNA is to be the primary molecule

responsible for holding gene;c informa;on,
then it must have three important
characteris;cs

It must hold vast amounts of informa;on

The molecule must be extremely stable
Must be easily replicated

DNA is able to hold vast amounts

informa;on in its sequence of nitrogenous
bases

Although there are only four nitrogenous

bases each gene can s;ll has its own
iden;ty

The number of bases varies for each gene

Sequence of bases varies for each gene
The reason why we say bases is that a gene
is only dened by the base sequence for only
one of the strands

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DNA Secondary Structure: The Structure Confers Stability

and Allows The Molecule To Hold Vast Amounts of
Informa;on

The stability of the double stranded DNA

molecule comes from two important forces

Hydrogen bonding between the base pairs

Base stacking interac;ons

In actuality, the base pairs lie at upon one

another and so instead of looking like
rungs on a ladder they look like a stack of
coins

The bases in DNA stack together, which

results in increased stability by elimina;ng
water from the interior of the DNA molecule

In order to have the base pairs lie at on

one another, each base pair must be slightly
twisted with respect to previous base pair

DNA Secondary Structure: The Structure Confers

Stability and Allows The Molecule To Hold Vast
Amounts of Informa;on

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DNA Secondary Structure: Important

Physical Features of the Double Helix

The shape of base pairs results in two

extremely important physical features

Major Groove
Minor Groove

The grooves are present because the two

bonds that a\ach a base pair to its
deoxyribose sugar rings are not directly
opposite (not a true 180 degrees)

The major and minor groove form as a

result of the angle at which the two sugars
protrude from the base pairs

120 degrees for the narrow angle (minor

groove forma;on)
240 degrees for the wide angle (major groove
forma;on

The major groove is about twice as wide (22

A) as the minor groove (12 A)

The grooves allow for proteins to bind to

the DNA

DNA Secondary Structure: Important

Physical Features of the Double Helix

Proteins that bind the DNA in a sequence

specic manner bind the major groove

Below are the pa\erns of donors and

acceptors for each of the four possible base
pairs (A= acceptor D = Donor H=non-polar
hydrogen M=methyl group)

The wide geometry of the major groove

allows proteins to gain access to the
sequence informa;on
Each base pair has its own unique
combina;on of hydrogen bond acceptors and
donors which line the edge of the major
groove

A-T (ADAM)
T-A (MADA)
G-C (AADH)
C-G (HDAA)

Proteins that bind the DNA in a sequence

non-specic manner o[en bind the minor
groove

Pa\erns of hydrogen bond acceptors and

donors lining the minor groove are incredibly
similar
For A-T or T-A base pairs (ADA)
For G-C or C-G base pairs (AHA)

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DNA Secondary Structure: Important Physical

Features of the Double Helix and Disease

Many diseases result from a changes in DNA

sequence that abrogate (block) DNA binding

The changes in DNA sequence result in a

change in the pa\ern of hydrogen bond
acceptors and donors in the major groove
The protein that is supposed to bind the DNA
in a sequence specic manner can no longer
do so because the pa\ern has changed

Familial Hypercholersterolemia (FH) is a

gene;c disorder caused by changes in DNA
sequence in the LDLR gene (Low-Density
Lipoprotein Receptor)

The LDLR gene encodes a protein that is

expressed in the liver and adrenal cortex

This protein encoded by the LDLR gene is

responsible for removing 66-80% of all LDL
from the blood

Pa;ents with FH exhibit disease symptoms

at birth star;ng with a cholesterol level
above the 95 percen;le

DNA Secondary Structure: Important Physical

Features of the Double Helix and Disease

By the second decade of life, other

secondary symptoms arise due to
the extremely high cholesterol levels

Arcus Cornae
Tendon Xanthomas
Recurrent nonprogressive polyarthri;s
Tenosynovi;s
Artheroschlerosis

Without aggressive treatment,

pa;ents can die of secondary
symptoms by age 30

There is no cure for FH, pa;ents

require aggressive normaliza;on of
LDL levels
Dietary management
Drug therapy to reduce the amount of
free LDL in the blood

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DNA Secondary Structure: Important Physical

Features of the Double Helix and Disease

There are two iden;ed changes in the

sequence of the LDL gene that can result in
loss of a specic protein called from Sp1
from specically binding the DNA encoding
LDLR gene

One is a change from a C-G base pair G-C

base pair at a specic posi;on (-139)
The other is a change from a C-G base pair
T-A base pair at another specic posi;on
(-60)

A pa;ent needs only one of these changes

to lose Sp1 binding, which will lead to FH
development

Each of these base changes in DNA

sequence will change the pa\ern of
hydrogen bond acceptors and donors in the
the major groove

For the C-G G-C change, (HDAA AADH)

For the C-G T-A change (HDAA MADA)

DNA Secondary Structure: DNA Can Form

Mul;ple Types of Double Helices

When Watson and Crick determined the secondary

structure of DNA, it was thought to be fairly simple
without signicant structural varia;on between
DNA molecules

As it turns out that is not quite true as DNA can

adopt mul;ple conforma;ons

The three conforma;ons DNA forms are as follows

B-DNA
A-DNA
Z-DNA

The DNA conforma;on present is generally

determined by condi;ons of the solu;on in which
the DNA is present in (or experimentally, the
condi;ons in which crystallized)

Some of these conforma;ons are physiologically

relevant
Some of these conforma;ons are not physiologically
relevant

Salt Concentra;on
Water Content (humidity)

Each conforma;on will have its own structural

proper;es

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DNA Secondary Structure: DNA Can

Adopt A B-Type Double Helix (B-DNA)

The B-DNA form is considered the Watson and

Crick conforma;on and is the most predominant
conforma;on in vivo

The B-form of DNA is seen when the DNA is

present in condi;ons of high humidity (> 95%) and
rela;vely low salt

The B-DNA forms a right handed double helix (has

a right handed twist)

The grooves present in B-DNA have the following

characteris;cs

In B-DNA, the major groove is wide and of moderate

depth
In B-DNA the minor groove is also of moderate depth,
but is narrower

The distance between base pairs is about 0.34 nm

For each turn of the helix there will be 10.5 bp/

turn at a distance of approximately 3.4 nm

DNA Secondary Structure: DNA Can Adopt

an A-Type Double Helix (A-DNA)

The A-DNA form can be observed if the

water content is decreased and the salt
concentra;on is increased during
crystalliza;on

The A-form has only been observed in vitro

and is thus thought to not be physiologically
relevant

The A-DNA form takes the shape of a right-

handed double helix

The A-DNA form is more compact and

slightly ;lted

The bases are ;lted with respect to the axis

There are 11 bases per turn

The grooves of A-DNA have the following

geometry

The major groove is deep and narrow

The minor groove is shallow and broad

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DNA Secondary Structure: DNA Can Adopt an Z-

Type Double Helix (Z-DNA)

The Z-form of DNA was discovered by the

Alexander Rich Lab in 1979 (MIT)

Z-DNA was visualized in the laboratory when the

DNA was crystallized under one of two condi;ons

DNA crystallized under high-salt condi;ons

DNA crystallized in the presence of alcohol

The Z-form of DNA can be present under

physiological condi;ons when the DNA has long
stretches of alterna;ng guanine and cytosine

The Z-DNA is a le[ handed double helix, and turns

in a counter-clockwise fashion when viewed down
its axis

The le[-handedness of the helix occurs due to

alterna;ng syn and an; conforma;ons of the n-
glycosidic bond in consecu;ve G-C nucleo;des

The backbone of the Z-DNA has a zig-zag

appearance

The Z-DNA grooves have the following

characteris;cs

The major groove is shallow, almost to the point of

being non-existent
The minor groove is deep and narrow

DNA Secondary Structure: DNA Can

Adopt an Z-Type Double Helix (Z-DNA)

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Strand Denatura;on and DNA

Renatura;on: Introduc;on

This ability of DNA to denature and renature

is important for two biological processes

Replica;on (in vivo)

Gene expression-transcrip;on (in vivo)

Nucleic acid denatura;on is important for a

number of experimental techniques in
Molecular Biology

The two strands are held together by

hydrogen bonds

Hydrogen bonds are considered weak non-

covalent forces
Allows for the two strands to come apart
really easily

If the DNA is heated just above physiologic

temperature (near 100 C) or subjected to
high pH, the DNA denatures (the two
strands separate)

If the solu;on containing the DNA is slowly

cooled, the DNA can renature (The two
complementary strands can re-form regular
double helices)

Strand Denatura;on and DNA

Renatura;on: Introduc;on
In the lab if DNA is heated just
above physiologic temperature:

The DNA denatures (the two

strands separate)
If the solu;on is slow cooled, the
two complementary strands
renature (form regular double
helices)

If the pH of the solu;on is

increased:
The DNA denatures because most
other bases form hydrogen bonds
more readily than nitrogenous
bases
If the solu;on is slowly re-
acidied, the two complementary
strands can re-form regular double
helices

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Strand Denatura;on and DNA

Renatura;on: Introduc;on
The process of adding heat to
denature the DNA only aects
the hydrogen bonds (weak
bonds) that allow base pairing to
occur
The phosphodiester bonds are
covalent linkages which are
much stronger than hydrogen
bonds and are unaected by
temperature
Enzyma;c ac;vity is needed to
break phosphodiester linkages
DNases
Restric;on Endonucleases

Strand Denatura;on and DNA

Renatura;on: Denatura;on Kine;cs

Important insights into the proper;es of

the double helix were obtained through
classic experiments carried out in the 1950s
on denatura;on kine;cs

In order to follow DNA denatura;on,

ultraviolet light at a wavelength () of 260
nm is used

DNA maximally absorbs light at a

wavelength of 260 nm due to the
nitrogenous bases

Single stranded DNA absorbs UV light at =

260 nm more eciently than double
stranded DNA

Base stacking of double-stranded DNA

quenches the ability of the DNA to absorb UV
light
Na;ve double-stranded DNA will absorb
about 40% less UV light as compared to the
same amount of single stranded DNA

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Strand Denatura;on and DNA

Renatura;on: Denatura;on Kine;cs

To study denaturata;on kine;cs, a solu;on

of double stranded DNA is subjected to heat

Plot absorbance as a func;on of

temperature

Temperature is on the X-axis

Absorbance is on the Y-axis

As the solu;on is heated, the op;cal density

(absorbance) at 260 nm markedly increases
within a small range

This phenomenon known as hyperchromicity

Hyperchromicity: an increase in absorbance
of light by a molecule at a given wavelength

The midpoint of the transi;on from double

stranded to single stranded DNA is known
as the mel;ng temperature or Tm

The mel;ng temperature denotes the point

at which 50% of DNA in solu;on is single-
stranded

Strand Denatura;on and DNA

Renatura;on: Denatura;on Kine;cs
Mel;ng temperature is
dependent on the composi;on
of base pairs in a DNA molecule
G:C base pairs contain 3 H bonds
A-T base pairs contain 2 H bonds

The more G-C base pairs, the

higher the mel;ng temperature
The less A-T base pairs, the
lower the mel;ng temperature
Tm = 3(G-C base pairs) + 2 (A-T
base pairs)

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RNA Structure: Introduc;on

RNA is chemically similar to DNA with a couple of

major dierences

Single stranded
Can also base pair and form signicant secondary
structure

Instead of base pairing with a second strand, a

single RNA strand can base pair with itself

The structure of RNA is breathtakingly intricate

and graceful -Harry Noller (2005)

There are many types of RNA that can adopt

signicant number of structures that are important
for biological func;on

tRNA (transla;on)
rRNA (ribosomal RNA)
snRNA (splicing)
snoRNA (rRNA processing)
Ribozymes (enzyma;c func;on)
mRNA (gene regula;on)

The signicant secondary structural mo;fs are

stabilized by base pairing

Conven;onal base pairing (Watson-Crick)

Unconven;onal base pairing

RNA Structure: DNA and RNA

Structure Comparison

The structure of RNA and DNA are

fundamentally quite similar, with
and one signicant chemical
dierence

Below are some similari;es:

Below are the dierences:

Each is synthesized from the monomer

building block-nucleo;des
Nucleo;des are polymerized in exactly
the same way

RNA is generally found as a single

stranded molecule: Has only 1
phosphodiester backbone (what makes
RNA single stranded)
The basic building blocks (nucleo;des)
of RNA and DNA are slightly dierent
(sugar and nitrogenous bases)
RNA is more chemically reac;ve

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RNA Structure: Ribonucleo;de Structure

and The Pentose Sugars
The Dierences between
Deoxyribose and Ribose:

Dier in structure only by the

presence or absence of a 2
hydroxyl group
For RNA, the 2 carbon has a
hydroxyl group bound to it
For DNA, the 2 carbon does not
have a hydroxyl group (deoxy)
bound, instead it has a hydrogen
bound to it

The presence of the 2OH in

ribose gives DNA and RNA
dierent chemical proper;es

Hydroxyl group is more reac;ve

than the hydrogen
RNA can fold into a greater array
of structures
Allows RNA to form a whole array
of dierent types of base pairs
DNA is more stable than RNA;
RNA is more prone to degrada;on

RNA Structure: Base Pairing Is Cri;cal For

Allowing Secondary Structure To Form

The conven;onal base pairs found in RNA are as

follows (Watson-Crick Base Pairs):

In order for a single strand of RNA to base pair with

itself, non-canonical base pairing is also cri;cal

G:C base pair (3 H bonds)

A:U base pair (2 H bonds)

More than 20 types of non-canonical base pairs form

with at least two H bonds
The most common non-canonical base pair is the G-U
base pair (will be present in almost all secondary
structure) and base pairs through 2 H bonds
In Non-canonical base pairing one of the nitrogenous
bases of the pair will be shi[ed sideways to allow for
hydrogen bonds to form

Other less common non-canonical base pairs found

in RNA secondary structure are as follows

AU reverse Hoogstein (Adenine is shi[ed sideways in

comparison to the canonical AU base pair)
Sheared G-A base pair(2 H bonds)
G-A imino (3 H bonds) (note: 2 purines)

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RNA Secondary Structure: Base-Paired RNA

Adopts an A-type Helix

RNA readily forms secondary structure in

the form of a helix

RNA adopts an A-type helix congura;on

DNA cannot adopt an A-Type Helix under

physiological condi;ons
RNA can adopt an A-Type double helix under
physiological condi;ons

The RNA A-Type Helix cannot adopt a B-

conforma;on due to the 2OH group

The A-Type Helix RNA adopts is stabilized by

the same forces as the DNA B-Type Double
Helix

Hydrogen bonding between the base pairs

Base stacking interac;ons

RNA Secondary Structure: Base-

Paired RNA Adopts an A-Type Helix

The RNA A-Type Helix has 11

base pairs per turn and two
grooves
Major Groove
Minor Groove

The major groove is deep and

narrow and is not well suited
to protein-RNA interac;ons
The minor groove is shallow
and wide and is much be\er
suited to protein-RNA
interac;ons due to the
presence of 2 OH groups that
extend out into the minor
groove

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RNA Secondary Structure: Base-

Paired RNA Adopts an A-Type Helix

OH groups in the minor groove, RNA

binding proteins are unable to bind
there in a sequence specic manner
Many 2 OH groups do not allow for
iden;ca;on of specic base pairs
RNA binding proteins instead iden;fy
specic structures in the RNA

When two complementary stretches

of sequence are near each other, a
stem-loop structure may form
Not all sequences within the stretches
are complementary (especially at the
end)
Intervening, non-complementary
sequence is looped out from the
double-helical segment as a hairpin,
bulge or simple loop
If mispairing occurs on one side of the
helix
If mispairing occurs on both sides

Depending on the amount and loca;on

of the non-complementary sequence,
there are many varia;ons on the stem-
loop

RNA Secondary Structure: Base-

Paired RNA Adopts an A-Type Helix

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RNA Structure: Overview of Ter;ary

Structure

Beyond secondary structure, RNA can form higher

order ter;ary structure

RNA binding proteins can recognize specic por;ons

of an mRNA due to higher order 3-dimensional
structure
The higher order 3D structure allows for proper
func;ons of certain RNA (eg tRNA , rRNA, ribozymes)

Ter;ary structures can arise from the interac;on of

mul;ple secondary structures making use of
signicant non-conven;onal base pairing

tRNA
rRNA
snRNA

In some cases proteins are necessary to allow for

the forma;on of higher order ter;ary structure

Below are several common examples of ter;ary

structure

Pseudoknot Mo;fs
A-Minor Mo;f
Tetra-loop Mo;f
Ribose Zipper Mo;f
Kink-turn mo;f

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