Download exploring protein structure

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
complete activities using Cn3D to view proteins.
Save this Power Point to your desktop prior to beginning the show.
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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
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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 – haemoglobin and myosin
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Proteins for cell motility – proteins can link together to form
filaments that make movement possible.
Above: Myosin (red) and actin filaments
(green) in coordinated muscle contraction.
Right: Actin bound to the myosin binding
site (groove in red part of myosin protein).
Add energy 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
Tubulin
forms
helical
filaments
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
The cell cytoskeleton contains
microtubules that can contract to make cell
movement possible. Microtubules are
composed of filaments of the protein, tubulin
(far left). They form an alpha helix that
behaves a little like a ‘spring’ allowing
filaments to ‘stretch and contract’. This is
how cells control movement of their
organelles, of chromosomes in cell division
and of flagella and cilia.
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Proteins with catalytic behaviours - Enzymes
Catalase catalyses 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 activation energy for forming
the products water and oxygen from the substrate molecule hydrogen peroxide.
No catalyst =
Input of 71kJ energy required
Energy
Activation
Energy
With catalase
= Input of 8 kJ energy required
Substrate
Progress of reaction
Product
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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
them to absorb glucose for use or for storage as
glycogen in the liver.
Proteins in cell 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.
Source: http://genetics.nbii.gov/Basic1.html
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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 (vegie 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 (see slide 12)
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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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
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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
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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Exploring the 3D Structure of
Haemoglobin
We will now explore the structure of Haemoglobin using Cn3D. Click on
the button to get the instructions on how to do this
Instructions for viewing Cn3D
To complete this activity, you must have Cn3D installed on your computer.
If you do not have Cn3D installed on your computer you can download this
free application from the URL
http://ncbi.nih.gov/Structure/CN3D/cn3d.shtml
Click here to view Haemoglobin in Cn3D
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