EXPLORING PROTEIN
STRUCTURE
A teaching tool for introducing students to protein structure.
The final slide contains links to the files and programs students need to view
proteins using Cn3D.
Save this Power Point to your desktop prior to beginning the show.
1
Proteins….
If there is a job to be
done in the molecular
world of our cells,
usually that job is done
by a protein.
A protein hormone which helps to
regulate your blood sugar levels
CATALASE
An enzyme which removes
Hydrogen peroxide from your body
so it does not become toxic
Examples of proteins include hormones acting as
messengers; enzymes speeding up reactions; cell
receptors acting as ‘antennae’; antibodies fighting foreign
invaders; membrane channels allowing specific molecules
to enter or leave a cell; they make up the muscles for
moving; let you grow hair, ligaments and fingernails; and
let you see (the lens of your eye is pure crystalised
protein).
Source:
http://courses.washington.edu/conj/protein/insulin2.gif
http://www.biochem.ucl.ac.uk/bsm/pdbsum/1gwf/main.html
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Proteins can be fibrous
or globular
Let’s explore the diversity of protein structure and function by
investigating some examples
3
Fibrous proteins have a structural role
•Collagen
is the most abundant protein in
vertebrates. Collagen fibers are a major
portion of tendons, bone and skin. Alpha
helices of collagen make up a triple helix
structure giving it tough and flexible
properties.
•Fibroin
fibers make the silk spun by spiders
and silk worms stronger weight for weight
than steel! The soft and flexible properties
come from the beta structure.
•Keratin
is a tough insoluble protein that
makes up the quills of echidna, your hair and
nails and the rattle of a rattle snake. The
structure comes from alpha helices that are
cross-linked by disulfide bonds.
Source:http://www.prideofindia.net/images/nails.jpg
http://opbs.okstate.edu/~petracek/2002%20protein%20structure%20function/CH06/Fig%2006-12.GIF
http://my.webmd.com/hw/health_guide_atoz/zm2662.asp?printing=true
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The globular proteins
The globular proteins have a number of biologically important roles. They
include:
Cell motility – proteins link together to form filaments which make movement
possible.
Organic catalysts in biochemical reactions – enzymes
Regulatory proteins – hormones, transcription factors
Membrane proteins – MHC markers, protein channels, gap junctions
Defense against pathogens – poisons/toxins, antibodies, complement
Transport and storage – hemoglobin and myosin
5
Proteins for cell motility
Above: Myosin (red) and actin filaments
(green) in coordinated muscle contraction.
Right: Actin bound to the mysoin binding
site (groove in red part of myosin protein).
Add energy (ATP) and myosin moves,
moving actin with it.
Source: http://www.ebsa.org/npbsn41/maf_home.html
http://sun0.mpimf-
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Proteins in the Cell Cytoskeleton
Eukaryote cells have a cytoskeleton made up of straight hollow
cylinders called microtubules (bottom left).
Tubulin
forms
helical
filaments
They help cells maintain their shape, they act like conveyer belts
moving organelles around in the cytoplasm, and they participate in
forming spindle fibres in cell division.
Microtubules are composed of filaments of the protein, tubulin (top
left) . These filaments are compressed like springs allowing
microtubules to ‘stretch and contract’.
13 of these filaments attach side to side, a little like the slats in a
barrel, to form a microtubule. This barrel shaped structure gives
strength to the microtubule.
Source:
heidelberg.mpg.de/shared/docs/staff/user/0001/24.php3?department=01&LANG=en
http://www.fz-juelich.de/ibi/ibi-1/Cellular_signaling/
http://cpmcnet.columbia.edu/dept/gsas/anatomy/Faculty/Gundersen/main.html
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Proteins speed up reactions - Enzymes
2
2
Catalase speeds up the
breakdown of
hydrogen peroxide,
(H2O2) a toxic by
product of metabolic
reactions, to the
harmless substances,
water and oxygen.
The reaction is extremely
rapid as the enzyme
lowers the energy
needed to kick-start
the reaction (activation
energy)
+
No catalyst =
Input of 71kJ energy required
Energy
Activation
Energy
With catalase
= Input of 8 kJ energy required
Substrate
Product
Progress of reaction
8
Proteins can regulate metabolism – hormones
When your body detects an increase in the sugar
content of blood after a meal, the hormone
insulin is released from cells in the pancreas.
Insulin binds to cell membranes and this triggers the
cells to absorb glucose for use or for storage as
glycogen in the liver.
Proteins span membranes –protein channels
The CFTR membrane protein is an ion channel that
regulates the flow of chloride ions.
Not enough of this protein gets inserted into the
membranes of people suffering Cystic fibrosis. This causes
secretions to become thick as they are not hydrated. The
lungs and secretory ducts become blocked as a
consequence.
Source: http://www.biology.arizona.edu/biochemistry/tutorials/chemistry/page2.html
http://www.cbp.pitt.edu/bradbury/projects.htm
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Proteins Defend us against pathogens –
antibodies
Left: Antibodies like IgG found in
humans, recognise and bind to
groups of molecules or epitopes
found on foreign invaders.
Right: The binding site of an antigen
protein (left) interacting with the
epitope of a foreign antigen (green)
Source: http://www.biology.arizona.edu/immunology/tutorials/antibody/FR.html
http://tutor.lscf.ucsb.edu/instdev/sears/immunology/info/sears-ab.htm
http://www.spilya.com/research/
http://www.umass.edu/microbio/chime/
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Making Proteins
How are such a diverse range of proteins possible? The code for making a protein is
found in your genes (on your DNA). This genetic code is copied onto a messenger
RNA molecule. The mRNA code is read in multiples of 3 (a codon) by ribosomes
which join amino acids together to form a polypeptide. This is known as gene
expression.
Source: http://genetics.nbii.gov/Basic1.html
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The protein folds
to form its
working shape
Gene Expression
Gene
DNA
G T
NUCLEUS
Chromosome
CELL
A C T A
The order of bases in
DNA is a code for
making proteins. The
code is read in groups of
three
Cell machinery
copies the code
making an mRNA
molecule. This
moves into the
cytoplasm.
Ribosomes read the
code and accurately
AUGAGUAAAGGAGAAGAACUUUUCACUGGAUA join Amino acids
together to make a
S
L F T
M
E
E
protein
K
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The building blocks
The amino acids for making new proteins come from
the proteins that you eat and digest. Every time you
eat a burger (vege or beef), you break the proteins
down into single amino acids ready for use in
building new proteins. And yes, proteins have the
job of digesting proteins, they are known as
proteases.
There are only 20 different amino acids but they can
be joined together in many different combinations
to form the diverse range of proteins that exist on
this planet
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Amino Acids
An amino acid is a relatively small molecule with characteristic groups of
atoms that determine its chemical behaviour.
The structural formula of an amino acid is shown at the end of the animation
below. The R group is the only part that differs between the 20 amino acids.
Phenylalanine
Cysteine
Alanine
Glycine
Valine
Amino
H3H
C
H N
H
S
H H
CH
3
C
H H
R
C C O H
H O
Acid
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The 20 Amino Acids
The amino acids each have their own shape and charge
due to their specific R group.
View the molecular shape of amino acids by clicking on
the URL link below:
http://sosnick.uchicago.edu/amino_acids.html
Would the shape of a protein be affected if the wrong
amino acid were added to a growing protein chain?
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Making a Polypeptide
R
H2N
C
H
O H
H N
C
O
Peptide Bond
R
H2N
C
O
N
C
C
O¯H
H
H N
R
Peptide Bond Peptide Bond
H
C
O
O
C
R
C
H
N
O H
R
H
C
C
H N
C
C
O H
O
R
R
C
O
O H
O H
C
O
Polypeptide
Growth
Polypeptide production = Condensation Reaction
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Why Investigate Protein Structure?
Proteins are complex molecules whose
structure can be discussed in terms of:
primary structure
secondary structure
tertiary structure
quaternary structure
The structure of proteins is important as
the shape of a protein allows it to
perform its particular role or function
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Protein Primary Structure
The primary structure is the sequence of amino acids that are linked
together. The linear structure is called a polypeptide
http://www.mywiseowl.com/articles/Image:Protein-primary-structure.png
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Protein Secondary Structure
The secondary structure of proteins consists of:
alpha helices
beta sheets
Random coils – usually form the binding and active sites of proteins
Source: http://www.rothamsted.bbsrc.ac.uk/notebook/courses/guide/prot.htm#I
19
Protein Tertiary Structure
Involves the way the random coils, alpha
helices and beta sheets fold in respect to
each other.
This shape is held in place by bonds such as
•
weak Hydrogen bonds between amino
acids that lie close to each other,
•
strong ionic bonds between R groups
with positive and negative charges, and
•
disulfide bridges (strong covalent S-S
bonds)
Amino acids that were distant in the primary
structure may now become very close to
each other after the folding has taken
place
Source: io.uwinnipeg.ca/~simmons/ cm1503/proteins.htm
The subunit of a more complex protein has
now been formed. It may be globular or
fibrous. It now has its functional shape or
conformation.
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Protein Quaternary Structure
This is packing of the protein subunits to
form the final protein complex. For
example, the human hemoglobin
molecule is a tetramer made up of
two alpha and two beta polypeptide
chains (right)
Source: www.ibri.org/Books/
Pun_Evolution/Chapter2/2.6.htm
This is also when the protein associates
with non-proteic groups. For example,
carbohydrates can be added to form a
glycoprotein
Source:
www.cem.msu.edu/~parrill/movies/neur
am.GIF
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Explore your proteins
Scientists have worked out the shape of many proteins by
conducting experiments. When they have their results, they
publish them and this information is then entered into
supercomputing systems for people to access.
You can view the three dimensional structure of some of your
proteins using the computer program Cn3D. If you do not have
Cn3D installed on your computer you can download this free
application from the URL link:
Download Cn3D
Haemoglobin
Amylase
Collagen
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Research another protein. Discuss what you can learn about
its structure, function and the organism it comes from using
the skills you learned today and website resources.
You can explore a number of proteins using Cn3D. Go to the following
URL:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
In the “for” box, try some of the proteins listed below (one at a time)
and then hit “go”. You will get a list of options. Click on the writing in
blue to select one. A new page will appear. Click on the View 3D
structure button. Explore using your Cn3D skills.
Misc
Enzymes
Genetics
Toxins
Collagen
Amylase
Endonuclease
Ricin
Tubulin
Rubisco
Taq DNA Polymerase
Arsenic
Porphyrin
Pepsin
Ribosome
Tetanus toxin
Prion
Alcohol dehydrogenase
Helicase
Funnel web toxin
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