Lecture 3

• Governments act rationally by


  Placing the interests of the people they serve first in order to maximise their welfare
• Rationality in classical economic theory is a flawed assumption as people usually don't act rationally
• If you add up marginal utility for each unit you get total utility
• Protein sorting


  The process by which proteins are directed to specific cellular compartments or organelles
• Proteins are nuclear encoded
• mRNA arrives in the cytoplasm
• Translation starts on ribosomes in the cytosol
• Cytosolic proteins


  Proteins that stay in the cytosol with no special sorting signal
• Sorting signal/Signal sequence


  A stretch of amino acid sequence in a protein that directs the protein to a specific cellular compartment
• Sorting signals are not something separate added on, but are part of the protein sequence
• How specific proteins are sorted to different organelles

  1. Sorting signals are recognized by sorting receptors

  2. Sorting receptors sort proteins to their correct destinations
• Examples of organelles proteins can be sorted to

  • Nucleus
  • Mitochondria
  • ER
  • Peroxisomes
• Post-translational sorting


  Proteins are fully synthesized in the cytosol before being sorted to their destination
• Co-translational sorting


  Proteins are sorted to their destination during translation
• For post-translational sorting, proteins destined for the nucleus, peroxisomes, mitochondria, and chloroplasts are folded first before sorting
• For post-translational sorting, proteins destined for the nucleus, peroxisomes, mitochondria, and chloroplasts are unfolded until after sorting
• Nuclear localization signal


  A specific amino acid sequence that directs a protein to the nucleus
• The nuclear import receptor recognizes the nuclear localization signal and transports the protein into the nucleus through nuclear pores
• Nuclear localization signal


  Sequence of amino acids that tells the cell to take the protein to the nucleus
• Nuclear import receptor


  Protein that recognizes the nuclear localization signal and takes the protein to the nucleus
• Nuclear localization signal experiment

  1. Protein with nuclear localization signal goes to nucleus

  2. Protein with mutated nuclear localization signal stays in cytosol
• Many proteins go to the nucleus, including DNA polymerase and proteins that activate transcription
• Peroxisome import sequence


  Sequence of amino acids that tells the cell to take the protein to the peroxisome
• Peroxisomal import receptor


  Protein that recognizes the peroxisome import sequence and takes the protein to the peroxisome
• Peroxisomes contain enzymes for oxidative reactions, detoxification, and fatty acid breakdown
• Mitochondrial/chloroplast signal sequence


  Sequence of amino acids that tells the cell to take the protein to the mitochondria or chloroplast
• Sorting receptor


  Protein that recognizes the mitochondrial/chloroplast signal sequence and takes the protein to the organelle
• Hsp70 chaperone


  Protein that helps other proteins fold, but also keeps them unfolded for import into organelles
• Most mitochondrial and chloroplast proteins are nuclear-encoded and imported post-translationally
• Co-translational protein sorting


  Proteins are associated with the ER during translation, with an ER signal sequence guiding them into the ER
• ER signal sequence


  Hydrophobic sequence of amino acids that targets proteins for entry into the ER
• Rough ER


  ER with ribosomes attached, for synthesis of soluble and transmembrane proteins
• Smooth ER


  ER without ribosomes, for phospholipid synthesis and detoxification
• Co-translational translocation


  Protein is translocated into the ER lumen or membrane as it is being synthesized by ribosomes
• Soluble proteins


  Proteins that are transported into the ER lumen
• Transmembrane proteins


  Proteins that are inserted into the ER membrane
• Co-translational protein sorting to the ER


  1. Ribosome binds to mRNA encoding ER protein

  2. ER signal sequence emerges from ribosome

  3. Signal recognition particle (SRP) binds to signal sequence, arresting translation

  4. SRP-ribosome-nascent chain complex binds to SRP receptor on ER

  5. Translocon opens to allow protein entry into ER
• 1. terminal ER signal sequence


  Hydrophobic stretch of amino acids at the N-terminus that is removed by signal peptidase
• Not all proteins that enter the ER are released into the ER Lumen, some remain embedded in the ER membrane as transmembrane proteins
• The membrane bound ribosome will be omitted to illustrate the translocation of transmembrane proteins into the ER membrane