BMS 300 Lectures 3 and 4

Liposomes

  • Liposomes are spherical structures where phospholipid head groups point towards water both outside and inside, creating a stable formation.
  • They are not typically found in biology but are used in experiments.
  • RNA vaccines use liposomes to deliver RNA to cells, which then produce viral proteins and mount an immune response.

Micelles vs. Liposomes

  • Micelles consist of a single layer of phospholipids with tails pointed inward.
  • They are unstable because water molecules can disrupt the head groups causing the structure to fall apart.
  • Liposomes have a bilayer structure, with head groups facing water on both sides.

Liposome Size and Curvature

  • Liposomes range from 50 to 500 nanometers.
  • Typical cells are around 10 micrometers (10,000 nanometers) in diameter.
  • Small structures have high curvature.
  • As liposomes grow, they form planar bilayers with minimal curvature from one phospholipid to the next.

Analogy to Earth's Curvature

  • Each phospholipid head group is approximately one nanometer.
  • A cell with a 10-micrometer diameter has a circumference of about 30,000 nanometers.
  • The Earth's equator is about 24,500 miles; locally it appears flat, similar to how a large planar bilayer appears flat despite its curvature.

Lipid Mosaic Model of the Membrane

  • Biological membranes consist of a planar bilayer of phospholipids punctuated by transmembrane proteins.
  • This arrangement is known as the lipid mosaic model.
  • Proteins are polymers of amino acids linked by peptide bonds.

Basic Amino Acid Structure

  • All amino acids have a common structure:
    • An amine group (nitrogen and two hydrogens).
    • A central carbon atom.
    • An R group that varies among the 20 different amino acids.
    • A carboxylic acid group (carbon with a double-bonded oxygen and an OH).

Peptide Bond Formation

  • Peptide bonds link amino acids together through a dehydration synthesis.
  • The hydroxyl group from the carboxylic acid of one amino acid combines with a hydrogen from the amine group of another amino acid to form water (H2OH_2O).
  • This generates a covalent bond between the nitrogen of one amino acid and the carbonyl carbon of the adjacent amino acid.

Primary Structure of Proteins

  • The primary structure is the sequence of amino acids in a polypeptide chain.
  • Proteins can have several hundred amino acids.
  • The amino terminus is one end of the molecule, and the carboxy terminus is the other end.

Orientation of Amino Acid Sequence

  • Proteins have an orientation due to the way amino acids are linked.
  • One end is the amino terminus, and the other is the carboxy terminus.
  • This nomenclature is critical for understanding protein structure.

Secondary Structure of Proteins

  • It results from hydrogen bonding within the protein.
  • Two main forms: alpha helix and beta pleated sheet.

Alpha Helix

  • Alpha-helical regions are often short.
  • Essential for proteins crossing the phospholipid bilayer.
  • The helix is stabilized by hydrogen bonds between amino hydrogens and carbonyl oxygens.
  • The pattern for hydrogen bonding is I+4, where the carbonyl oxygen of amino acid ii interacts with the hydrogen on amino acid i+4i + 4.
  • Analogy: spiral staircase where each step (amino acid) twists by approximately 100 degrees (3.6 amino acids per full turn) and rises by 0.15 nanometers.

Beta Pleated Sheet

  • The other form of secondary structure, involving hydrogen bonds between adjacent strands.
  • Can be arranged in parallel or antiparallel orientations.
  • Antiparallel arrangements have a repeating ROH pattern between strands.
  • Parallel arrangements have offset hydrogen bonds that are somewhat weaker due to the twist.

Common Amino Acids in Alpha Helices

  • m a l e k (Methionine, Alanine, Leucine, Glutamic acid, Lysine) are frequently found.
  • m a r k l (Methionine, Alanine, Arginine, Lysine, and Leucine) and are pretty similar.
  • Glycine and proline are typically avoided due to their tendency to introduce kinks.

Role of R Groups in Secondary Structures

  • R groups aren't required, but some are favored over others.
  • Hydrogen bonding between the amine hydrogen and carbonyl oxygen drives the structure.

Protein Structure Representation

  • Flat ribbon-like structures indicate beta sheets, with arrows showing direction (antiparallel or parallel).
  • Helices are often shown as twisted coils.
  • Proteins in aqueous environments tend to hide alpha helices between beta sheets to protect them from water's dipole moments.

Tertiary structure

  • Involves the three-dimensional shape of the protein.
  • Requires R groups, which are divided into those that are hydrophilic and hydrophobic.

Amino Acid Properties

  • Amino acids are classified as nonpolar (hydrophobic), polar, or charged (hydrophilic).

Amino Acid Structures

  • Glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan, and methionine are nonpolar.
  • Serine, threonine, cysteine, tyrosine, asparagine, and glutamine are polar.
  • Aspartate, glutamate, lysine, arginine, and histidine are charged.

Three Important Amino Acids

  • Serine, threonine, and tyrosine have hydroxyl groups and can be phosphorylated.
  • They're important in G protein-coupled receptors and kinases.
  • Glutamate is a common neurotransmitter in the nervous system.
  • Lysine and arginine have long side chains and are charged.
  • Histidine binds to metals.

Protein Folding

  • In aqueous environments, hydrophilic R groups point toward water, and hydrophobic R groups point inward, away from water.

Importance of Three-dimentional Shape

  • The three-dimensional shape of a protein determines its function.
  • It influences how antigens bind to antibodies and how neurotransmitters bind to receptors.

Representation of Protein Structure

  • Hydrophilic R groups (blue gumdrops) point outward, and hydrophobic R groups (white gumdrops) are folded inward.
  • This folding minimizes the interaction between hydrophobic residues and water.

Binding Pockets

  • The three-dimensional shape of an enzyme creates binding pockets for substrates.
  • The shape and charge of the binding pocket determine how substrates fit.

Myosin Example

  • Myosin is an enzyme that converts ATP to ADP plus inorganic phosphate.
  • It has a long tail and a head with an ATP-binding pocket.

ATP Binding

  • ATP has a ribose sugar, adenine, and a triphosphate group.
  • The triphosphate group is heavily charged.
  • For ATP to bind, it must match the charge and shape of the binding pocket.
  • Myosin cleaves ATP into ADP and inorganic phosphate in the binding pocket.
  • When the myosin head binds to actin, the ADP and inorganic phosphate leave, causing a structural change and movement.

Energy Conversion

  • Myosin converts chemical energy in ATP into mechanical energy in movement.
  • Charge changes in the binding pocket drive the movement.
  • The three-dimensional shape of the myosin head and its interaction with actin are crucial for this process.