Proteins Unit 1

• Proteome


  The entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time
• Genome


  All of the genetic material in a cell including DNA and RNA
• The proteome is greater than the number of genes


  Particularly in eukaryotes because more than one protein can be produced from a single gene as a result of alternative gene splicing
• Non-coding RNA genes


  Genes that do not code for proteins and include those that are transcribed to produce tRNA, rRNA, and RNA molecules that control the expression of other genes
• Factors affecting the set of proteins expressed by a given cell type

  • Metabolic activity of the cell
  • Cellular stress
  • The response to signalling molecules
  • Diseased versus healthy cells
• Synthesis and Transport of Proteins

  1. Ribosomes

  2. Nucleus

  3. Rough endoplasmic reticulum

  4. Smooth endoplasmic reticulum
• Rough endoplasmic reticulum (RER)


  Has ribosomes on its cytosolic face
• Smooth endoplasmic reticulum (SER)


  Lacks ribosomes
• Cytosolic ribosomes


  The synthesis of all proteins begins here, and the synthesis of cytosolic proteins is completed there
• Stages of Synthesis Membrane components by RER

  1. Proteins are synthesised by ribosomes in the cytoplasm

  2. A signal protein (SRP) from the membrane binds to the ribosome and stops translation

  3. The SRP binds to a receptor directs the ribosome to attach to the endoplasmic reticulum forming the RER

  4. Translation restarts and the protein is now inserted into membrane of the ER

  5. Once translation is finished, the ribosome detaches
• Movement of Proteins Between Membranes

  1. Proteins in the RER are transported and fuse with the Golgi apparatus

  2. As proteins move through the Golgi apparatus they undergo post-translational modification

  3. Molecules move through the Golgi in vesicles that bud off from one disc and fuse to the next one in the stack

  4. Enzymes catalyse the addition of various sugars in multiple steps to form the carbohydrates

  5. Vesicles move along microtubules to other membranes and fuse with them within the cell, they also take proteins to the plasma membrane and lysosome
• The Secretory Pathway


  1. Secreted proteins are translated in ribosomes on the RER and enter its lumen

  2. The proteins move through the Golgi apparatus and are then packaged into secretory vesicles

  3. These vesicles move to and fuse with the plasma membrane, releasing the proteins out of the cell

  4. Many secreted proteins are synthesised as inactive precursors and require proteolytic cleavage to produce active proteins
• Proteolytic cleavage


  Another type of post-translational modification where digestive enzymes and insulin are examples of secreted proteins that require proteolytic cleavage to become active
• Amino acid


  Monomers that are linked by peptide bonds to form polypeptides
• Types of amino acid R groups

  • Basic (Positively charged)
  • Acidic (Negatively charged)
  • Polar
  • Hydrophobic
• Basic (Positively charged) R groups

  Contain an amino side chain (-NH2), examples are Arginine, Histidine, Lysine
• Acidic (Negatively charged) R groups

  Contain a carboxylic acid side chain (-COOH), examples are Aspartic Acid, Glutamic acid (Glutamate)
• Polar R groups


  Hydrophilic, examples are Cysteine, Serine, Threonine, Tyrosine, Asparagine, Glutamine
• Hydrophobic R groups


  Also known as non-polar, avoid contact with liquids, examples are Alanine, Glycine, Isoleucine, Leucine, Methionine, Tryptophan, Phenylalanine, Proline, Valine
• Primary structure of proteins


  The sequence in which the amino acids are synthesised into the polypeptide
• Secondary structure of proteins


  The folding of the polypeptide chain into regular structures like alpha helices and beta sheets
• Basic amino acids


  • Arg: Arginine
  • His: Histidine
  • Lys: Lysine
• Acidic (Negatively charged) R Groups

  • Asp: Aspartic Acid
  • Glu: Glutamic acid (Glutamate)
• Polar R Groups


  • Cys: Cysteine
  • Ser: Serine
  • Thr: Threonine
  • Tyr: Tyrosine
  • Asn: Asparagine
  • Gln: Glutamine
• Hydrophobic R Groups


  • Ala: Alanine
  • Gly: Glycine
  • Ile: Isoleucine
  • Leu: Leucine
  • Met: Methionine
  • Trp: Tryptophan
  • Phe: Phenylalanine
  • Pro: Proline
  • Val: Valine
• Primary Structure


  The sequence in which the amino acids are synthesised into the polypeptide
• Secondary Structure


  • Hydrogen bonding along the backbone of the protein strand results in regions of secondary structure: Alpha helices, Parallel or antiparallel beta pleated sheets, Turns
• Tertiary Structure


  The polypeptide folds into a tertiary structure, stabilised by interactions between R groups such as: Hydrophobic interactions, Ionic bonds, London dispersion forces, Hydrogen bonds, Disulfide bridges – covalent bonds between R groups containing sulfur
• Quaternary Structure


  Quaternary structure exists in proteins with two or more connected polypeptide subunits, describing the spatial arrangement of the subunits
• Prosthetic group


  A non-protein unit tightly bound to a protein and necessary for its function
• Haemoglobin


  Iron-containing oxygen transporting protein present in the red blood cells of almost all vertebrates
• The ability of haemoglobin to bind to oxygen


  Is dependent upon the non-protein haem group
• Increasing temperature


  Disrupts the interactions that hold the protein in shape, causing the protein to unfold and become denatured
• Changes in pH


  Affect the charges on acidic and basic R groups, causing loss of normal ionic interactions between charged groups and gradual denaturation of the protein
• Ligand


  A substance that can bind to a protein
• As a ligand binds to a protein-binding site


  The conformation of the protein changes, causing a functional change in the protein
• Allosteric


  Interactions which occur between spatially distinct sites
• Allosteric proteins


  • The binding of a substrate molecule to one active site increases the affinity of the other active sites for binding of subsequent substrate molecules
  • Many allosteric proteins consist of multiple subunits which means they have a quaternary structure
• Co-operativity


  Changes in binding at one subunit alter the affinity of the remaining subunits
• Allosteric site


  A second type of site on allosteric enzymes where modulators bind to regulate the activity of the enzyme