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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.
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Proteins….
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.w ashington.edu/conj/protein/insulin2.gif
http://w w w.biochem.ucl.ac.uk/bsm/pdbsum/1gw f/main.html
If there is a job to be done in the molecular
world of our cells, usually that job is done
by a protein. CATALASE
An enzyme which removes Hydrogen peroxide from your body so it does not become toxic
A protein hormone which helps to regulate your blood sugar levels
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Proteins can be fibrous
or globular
Let’s explore the diversity of protein structure and function by investigating some examples
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Fibrous proteins have a structural role
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
•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.
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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
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Proteins for cell motility
Source: http://w w w.ebsa.org/npbsn41/maf_home.htmlhttp://sun0.mpimf-
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.
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Eukaryote cells have a cytoskeleton made up of straight hollow cylinders called microtubules (bottom left).
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.
Tubulin forms helical
filaments
Source:
heidelberg.mpg.de/shared/docs/staff/user/0001/24.php3?department=01&LANG=en
http://w w w.fz-juelich.de/ibi/ibi-1/Cellular_signaling/
http://cpmcnet.columbia.edu/dept/gsas/anatomy/Faculty/Gundersen/main.html
Proteins in the Cell Cytoskeleton
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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)
Energy
Progress of reaction
Substrate Product
No catalyst = Input of 71kJ energy required
Activation Energy
With catalase = Input of 8 kJ energy required
Proteins speed up reactions - Enzymes
+2 2
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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
Source: http://w w w.biology.arizona.edu/biochemistry/tutorials/chemistry/page2.html
http://w w w.cbp.pitt.edu/bradbury/projects.htm
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.
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Proteins Defend us against pathogens –
antibodies
Source: http://w w w.biology.arizona.edu/immunology/tutorials/antibody/FR.html
http://tutor.lscf.ucsb.edu/instdev/sears/immunology/info/sears-ab.htmhttp://w w w.spilya.com/research/
http://w w w.umass.edu/microbio/chime/
Left: Antibodies like IgG found in humans, recognise and bind to groups of molecules or epitopesfound on foreign invaders.
Right: The binding site of an antigenprotein (left) interacting with the epitope of a foreign antigen (green)
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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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G T A C T A
Chromosome
The order of bases in
DNA is a code for
making proteins. The
code is read in groups of
three
DNA
Gene
Cell machinery
copies the code
making an mRNA
molecule. This
moves into the
cytoplasm.
Ribosomes read the
code and accurately
join Amino acids
together to make a
protein
AUGAGUAAAGGAGAAGAACUUUUCACUGGAUA
M S E E LK TF
The protein folds
to form its
working shape
CELL
NUCLEUS
Gene Expression
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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 AcidsAn 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.
O
R
O
H
H
H
H N C C
H3C
CH3
C HC
H
H H
GlycineAlanineValineCysteinePhenylalanine
H
H
C
S
H HCH H
Amino 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
H2NC
O
C
R
C
O
CO‾H
R
N
H
HO H
O HH N
C
O
C
RH
O HH
C
O
C
R
N
H
NC
O
C
R
H2NC
O
C
R H
O HO HN
C
O
C
R
H2NC
O
C
R H
NC
O
C
RH
Peptide Bond Peptide BondPeptide Bond
Polypeptide production = Condensation Reaction
PolypeptideGrowth
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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 StructureThe secondary structure of proteins consists of:
alpha helicesbeta sheetsRandom coils – usually form the binding and active sites of proteins
Source: http://www.rothamsted.bbsrc.ac.uk/notebook/courses/guide/prot.htm#I
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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
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.
Source: io.uwinnipeg.ca/~simmons/ cm1503/proteins.htm
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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.cem.msu.edu/~parrill/movies/neur
am.GIF
This is also when the protein associates with non-proteic groups. For example, carbohydrates can be added to form a glycoprotein
Source: www.ibri.org/Books/
Pun_Evolution/Chapter2/2.6.htm
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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
CollagenHaemoglobin Amylase
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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 w eb toxin