In this lecture you will:

  • learn about 4 major post translation modifications of proteins

    Proteins become functional by folding into secondary, tertiary and even quarternary forms.  In addition to folding proteins can undergo post translation modifications  which can give them different functions.

    4 types of post translation modifications (excellent site HERE)
    1:  FOLDING

    As a protein chain is produced, it makes a PRIMARY structure which is just the sequence of the protein as it is made.  The primary structure is susceptible to being broken down.  So the a primary sequence rapidly folds up and when it does lots of weak hydrogen bonds form between amino acids that are close to each other in the chain



    It is the sequence and PROPERTY of THE R GROUPS ON THE amino acids that determine how they fold

    To get alpha and beta structures, the aa have to repeat in a very specific way.  Computers can now take an aa primary sequence and find these "runs" of aa and predict a lot about what the protein is going to look like.  Computers are still not able to predict ALL the folding patterns.
    the hydrogen bonding is weak, so it is disrupted by heat, acids or bases a process called denaturation

    HERE is a java that is interactive and allows the user to change conditions for folding proteins

    ALPHA HELIX is  a REGULAR folding that results in a helix stabilized by intra - aa hydrogen bonds. Helices are good for structural proteins like muscles. They are stabilized by hydrogen bonds between the helices.


    BETA SHEET OR PLEAT is also a regular folding that results in a zig zag form. They are stabilized by hydrogen bonds between the zig zags



    Alpha helices and beta sheets are often found together and this forms a TERTIARY STRUCTURE which is held together by hydrogen bonding.  These bonds lower the overall energy level and create a more stable molecule.  Tertiary folding creates structures that look GLOBULAR and are most often enzymes. They are stabilized by hydrogen bonds between the subunits.


    NOW, when two or more separate tertiary structures associate together it forms a QUARTERNARY structure. They are stabilized by hydrogen bonds between the individual units. 

    Hemoglobin, for example,  consists of four polypeptide chains, each with its own tertiary structure, fitting together into a larger globular structure held together by hydrogen bonds. 

    Other enzymes may be made of two or more DIFFERENT tertiary structures, like LDH, an enzyme of the heart. 

    proteolytic cleavage, simplest is removal of the initiation or initial methionine that starts all proteins

    -- many active proteins are inactive when they are first made... and only when there is a need for the active form is the protein cleaved in specific ways that activates the protein for some function.  such  inactive proteins are Insulin, pancreatic enzymes, enzymes involved in clotting .. are called pre-pro-proteins.  -- so, insulin is made and stored in the islet cells in the pancreas.  when sugar in the blood rises it triggers the islet cells to secrete it from the pancreas.  It is then cleaved and folds into pro-insulin which is further cleaved yielding active insulin composed  of two peptide chains linked together through disulfide bonds.

    --  Another example of a proteolyic enzyme is Papain, found in papaya and added to meat tenderizers that purchased at the store.  It is used to tenderize touch pieces of meat. 

    Most proteins secreted or bound to the plasma Membrane have carbohydrates attached to proteins.

    Glycoproteins on cell surfaces, for example, can be important for communication and recognition between cells and are thus involved in the immune system self-recognition. 

    Several viruses, bacteria and parasites use the cell-surface carbohydrates modified proteins as portals of entry into cells.  Malaria infect RBC using Duffy blood group antigens.

    ABO blood group antigens are on the surface of cells.  Some people also have their  ABO carbohydrates  associated with glycoproteins found free in the serum.  These are are  referred to as the  SECRETED forms.  In  forensic science, before DNA  fingerprinting, human fluids at crime scenes was tested for ABO AND whether it was secreted or not.

    Helicobacter pylori is the  bacterium responsible for chronic gastritis, ulcers and a common form of  cancer, adenocarcinoma.
    -- the bacteria attaches to the  Lewis blood group antigen which is found on the red blood cells of people with type O blood, but it also occurs on the gastric lining.  So people with O blood group are most susceptible to ulcers from bacteria than other blood groups.  Evidently, they are close to getting a vaccine to stop both the ulcers and cancers from this bacteria. 


    "In 1938, Arnold F. Willatt invented the cold wave, the precursor to the modern perm. It used no machines and no heat. The hair was wrapped on rods and a reduction lotion containing ammonium thioglycolate was applied. This chemical breaks open the disulfide linkages between the polypeptide bonds in the keratin (the protein structure) in the hair. The disulfide bonds give hair its elasticity, and can be reformed with chemicals. Next, an oxidation lotion was applied, (hydrogen peroxide), to close the disulfide bridges again and the hair was reformed to the shape of the rod. The entire process took 68 hours at room temperature."


    Function of proteins
    structural skin, hair, cartilage, nails, and muscles.
    regulatory enzymes
    cell processes  proteins sit in the cell membrane and act as gate-keepers letting the correct molecules in.. due to "lock and key" recognition
    immunity antibodies and other soluble proteins of the immune system
    carriers  of materials, for example, the protein hemoglobin carries oxygen to the cells

    Give the 3 post translation modifications we talked about and give an example of each?
    What kind of post transitional modification gives us our various blood groups?
    Why are people who get ulcers from H. pylori usually have the O blood group?
    Know the structure of amino acids.  Discuss what it is that makes some hydrophobic and some hydrophilic.
    Discuss protein folding primary thru quaternary.