Lecture 8

Is secondary structure important?

• Hair protein (keratin) is very rich in alpha-helical structures

  • hair stretches because it is easy to break the H-bonds that stabilize alpha-helices

• prions

  • misfolded proteins which induce normal versions of that protein to fold the same incorrect way

  • misfolded protein comes out of solution, creates plaques

  • causes family of diseases called spongiform encephalopathies (disease of the brain)

tertiary structure

• unique 3D folded structure

• final conformation of some proteins

• due to interactions between R-groups with each other and with backbone

• stabilized by

  • H-bonds between polar (or charged) side chains

  • H-bonds between hydrophilic side chains and backbone

  • Ionic bond between an acidic and basic amino aicd

  • hydrophobic clustering of non-polar side sides

    • van der Waals forces

  • disulfide linkages

    • covalent bonding in side chains

    • name of covalent bond that CAN participate in tertiary structure

    • is very intentional when bonded

• thousands of water molecules surround a protein, contorting the protein so that its hydrophilic R groups are on outside and hydrophobic R groups are on inside

• line up sites for functional activity of that protein

quaternary structure

• found in proteins with multiple polypeptide chains (subunits)

• subunits can be same or different

  • 2 identical subunits — homodimer

  • 2 different subunits — heterodimer]

  • ex: ferritin (iron storage protein) has 24 identical subunits

• example: hemoglobin

  • 4 separate polypeptides (2 alpha and 2 beta chains)

  • sickle cell mutation

    • changes a Glu (hydrophilic) to a Val (hydrophobic)

    • affected amino acid is on outside of protein

    • Hb molecules stick together to “hide” Val from water

    • oxygen levels fall, Hb precipitates, distorts red blood cells

relative stabilities of biomolecular forces

• covalent bond → disulfide linkages (very stable)

• ionic bonds → easily made and broken (only have to change pH or temp)

• hydrogen bonds and hydrophobic clusters are relatively the same strength

• van der Waals forces

removal or inactivation of stabilizing forces unfolds (denatures) the protein to primary structure, but no peptide bonds are broken

• all secondary and tertiary structure is broken

• almost always leads to loss of function

• acids/bases, heat, detergents

if denaturing agent is removed, some proteins will resume properly folded 3D structure

• “instructions” are in primary structure

many proteins are enzymes: biological catalysts; they facilitate biological reactions

• this is necessary because most cellular reactions proceed at a very slow rate

two broad categories of cellular reactions based on change in energy level (E):

• reactions that require an input of energy

• reactions that release energy upon completion

reactions that require energy are called biosynthetic or anabolic

• linking together of smaller molecules into larger ones, such as condensation reactions of monomers to macromolecules

reactions that release energy are called catabolic

• break down larger molecules into smaller ones, such as the hydrolysis reactions of macromolecules to monomers

• also referred to as spontaneous reactions

• energy released is often lost as heat

catabolic (energy-releasing) reactions require a certain amount of energy to get started

• energy of activation (or EA)

• could come from heat, but that would denature proteins