Proteins

Proteins

  • Proteins have diverse structures and functions

    • Each type of protein has a unique three-dimensional shape

  • Amino acids are the building blocks of proteins

    • Amino acids are organic molecules with an amino group and a carboxyl group

    • They are linked together by peptide bonds to form polypeptides

Amino acids

  • Alpha carbon in an amino acid is asymmetric

    • It has four different partners: an amino group, a carboxyl group, a hydrogen atom, and an R group

Protein functions

    • Enzymatic proteins

      • Function: Selective acceleration of chemical reactions

      • Example: Digestive enzymes catalyze the hydrolysis of bonds in food

    • Defensive proteins

      • Function: Protection against disease

      • Example: Antibodies inactivate and help destroy viruses and bacteria

    • Storage proteins

      • Function: Storage of amino acids

      • Example: Casein, the protein of milk, is the major source of amino acids for baby mammals

    • Transport proteins

      • Function: Transport of substances

      • Example: Hemoglobin, the iron-containing protein of vertebrate blood, transports oxygen from the lungs to other parts of the body

    • Hormonal proteins

      • Function: Coordination of an organism's activities

      • Example: Insulin, a hormone secreted by the pancreas, causes other tissues to take up glucose, thus regulating blood sugar concentration

    • Receptor proteins

      • Function: Response of cell to chemical stimuli

      • Example: Receptors built into the membrane of a nerve cell detect signaling molecules released by other nerve cells

    • Contractile and motor proteins

      • Function: Movement

      • Example: Motor proteins are responsible for the undulations of cilia and flagella. Actin and myosin proteins are responsible for the contraction of muscles

    • Structural proteins

      • Function: Support

      • Example: Keratin is the protein of hair, horns, feathers, and other skin appendages. Collagen and elastin proteins provide a fibrous framework in animal connective tissues

Amino acids

  • The 20 amino acids of proteins

    • Nonpolar side chains; hydrophobic

      • Glycine (Gly or G)

      • Alanine (Ala or A)

      • Valine (Val or V)

      • Leucine (Leu or L)

      • Isoleucine (Ile or I)

    • Polar side chains; hydrophilic

      • Methionine (Met or M)

      • Phenylalanine (Phe or F)

      • Tryptophan (Trp or W)

      • Proline (Pro or P)

    • Since cysteine is only weakly polar, it is sometimes classified as a nonpolar amino acid

      • Cysteine (Cys or C)

    • Electrically charged side chains; hydrophilic

      • Basic (positively charged)

        • Lysine (Lys or K)

        • Arginine (Arg or R)

        • Histidine (His or H)

      • Acidic (negatively charged)

        • Aspartic acid (Asp or D)

        • Glutamic acid (Glu or E)

Polypeptides

  • Polypeptides are amino acid polymers

    • The kind and sequence of amino acids determine the final shape and chemical characteristics of a polypeptide

    • Amino acids are linked together to form polymers through dehydration reactions

    • The resulting covalent bond between amino acids is called a peptide bond

    • Polypeptides have a unique linear sequence of amino acids

    • The polypeptide backbone is the repeating sequence of atoms

    • Polypeptides have different side chains (R groups) of amino acids

  • Protein structure and function

    • Proteins have intricate three-dimensional architecture

    • The amino acid sequence of a polypeptide determines its three-dimensional structure

    • Proteins can have different shapes and structures

    • A protein's specific structure determines its function

    • Proteins can recognize and bind to other molecules

    • Protein function is dependent on molecular order

Visualizing Proteins

  • Proteins can be represented in different ways depending on the goal of the illustration.

    • Three models of lysozyme are depicted: space-filling model, ribbon model, and wireframe model.

    • Each model emphasizes a different aspect of the protein's structure.

  • Simplified diagrams are useful when the focus is on the function of the protein, not the structure.

  • It is unnecessary to show the actual shape of insulin in a diagram when the focus is on its action in general.

Levels of Protein Structure

  • Proteins share three superimposed levels of structure: primary, secondary, and tertiary structure.

  • Quaternary structure arises when a protein consists of two or more polypeptide chains.

Levels of Protein Structure

  • Primary Structure

    • Linear chain of amino acids

    • Coils and folds

    • dictates secondary and tertiary b/c chemical nature of backbone and side chains (R groups) of amino acids along polypeptide

  • Secondary Structure

    • Result of hydrogen bonds between repeating parts of polypeptide backbone (not amino acid side chains)

    • w/ backbone, atoms have partial positive charge, so weak hydrogen bonds individually, but together strong enough to support shape

      • a helix

        • Delicate coil held together by hydrogen bonding between every fourth amino acid

        • Found in transthyretin polypeptide

        • Other globular proteins have multiple stretches of a helix

      • pleated sheet

        • Two or more segments of the polypeptide chain lying side by side

        • Segments are connected by hydrogen bonds between parts of the two parallel segments

        • Found in the core of many globular proteins

  • Tertiary structure:

    • Hydrophobic interaction contributes to tertiary structure

      • Nonpolar amino acid side chains cluster at the core of the protein, out of contact with water

      • Collagen is an example of a fibrous protein with hydrophobic interactions

    • Other interactions that stabilize tertiary structure

      • Van der Waals interactions between nonpolar side chains

      • Hydrogen bonds between polar side chains

      • Ionic bonds between positively and negatively charged side chains

    • Covalent bonds called disulfide bridges can further reinforce the shape of a protein

      • Formed by the bonding of cysteine side chains

      • Example: Hemoglobin, a globular protein with quaternary structure

  • Quaternary structure

    • overall protein structure that results from the aggregation of polypeptide subunits

    • Some proteins consist of multiple identical polypeptide subunits

    • Examples: Transthyretin protein (four identical polypeptides), collagen (three identical helical polypeptides)

Sickle-cell disease

  • A single amino acid substitution in a protein causes sickle-cell disease.

    • Primary, Secondary, and Quaternary Structures

    • Red Blood Cell Shape

    • Normal hemoglobin proteins do not associate with one another

    • Normal red blood cells are full of individual hemoglobin proteins, each carries oxygen

    • Hydrophobic interactions between sickle-cell hemoglobin proteins lead to their aggregation

    • Fibers of sickle-cell hemoglobin deform red blood cells into a sickle shape

    • Capacity to carry oxygen is greatly reduced

BioInteractive Sickle-Cell Disease: A Change in Primary Structure

  • Even a slight change in primary structure can affect a protein's shape and ability to function

  • Sickle-cell disease is caused by the substitution of valine for glutamic acid in the primary structure of hemoglobin

  • Changes in the physical and chemical conditions of a protein's environment can cause denaturation, where the protein unravels and loses its native shape

  • Denatured proteins are biologically inactive

  • Most proteins become denatured if transferred from an aqueous environment to a nonpolar solvent

  • Sickle-cell disease causes abnormal hemoglobin molecules to aggregate and deform red blood cells into a sickle shape

  • Patients with sickle-cell disease experience periodic "sickle-cell crises" where angular cells clog blood vessels

Denaturation and renaturation of a protein

  • High temperatures or various chemical treatments can denature a protein, causing it to lose its shape and function

  • If the denatured protein remains dissolved, it may renature when the chemical and physical aspects of its environment are restored to normal

Interview with Linus Pauling: Winner of the Nobel Prize in Chemistry and the Nobel Peace Prize

  • A unique shape determines a protein's specific function

  • Protein structure is determined by the interactions responsible for secondary and tertiary structures

  • Folding of the polypeptide chain into a three-dimensional shape occurs during protein synthesis

Denaturation

  • Hydrophobic regions of proteins face outward toward the solvent

  • Denaturation agents disrupt hydrogen bonds, ionic bonds, and disulfide bridges

  • Denaturation can result from excessive heat or chemicals

  • Denatured proteins become insoluble and solidify

  • Proteins in the blood denature at very high body temperatures

  • Denatured proteins can sometimes return to their functional shape when the denaturing agent is removed

  • Protein's primary structure determines its shape

  • Amino acid sequence determines where secondary structures can form, where disulfide bridges are located, where ionic bonds can form, etc.

Protein Folding in the Cell

  • Amino acid sequence for about 65 million proteins is known

  • Three-dimensional shape for almost 35,000 proteins is known

  • Protein folding is a complex process with intermediate structures

  • Primary structure does not reveal the stages of folding

  • Methods have been developed to track protein folding stages

  • Some proteins do not have a distinct 3-D structure until they interact with a target protein or molecule

  • Intrinsically disordered proteins account for 20-30% of mammalian proteins

  • Misfolding of polypeptides in cells is a serious problem associated with diseases