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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 complete activities using Cn3D to view proteins. 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 2 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 4 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 5 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- 6 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. 7 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 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 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 9 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/ 10 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 11 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 12 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 13 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 14 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 15 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 16 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 17 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. 18 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 19 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 20