Intracellular Compartments and Protein Sorting

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Chapter 12

• Intracellular Compartments and Protein Sorting

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How all of the 10,00020,000 kinds of proteins go
to the right destination?
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Intracellular compartments in eukaryotic cells

• The nucleus and the cytosol
• All organelles that function in the secretory and
  endocytic pathways
• Mitochondria
• Plastids

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Three fundamentally different ways of protein
translocation
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Two types of protein sorting signals
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Nucleus ??Cytosol transport
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Nuclear ??Cytosol transport

• Signal sequences are rich in the positively
  charged amino acids (R, K)
• Nuclear proteins can be transported through the
  pore complex in folded conformation
• GTP is required (Ran GTPase)
• Signal sequences often are not cleaved off after
  transport.

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Nuclear pore complex
Containing FG-repeats serve as binding sites for
the import receptors
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Nuclear localization signals are rich in the
positively charged amino acids
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Nuclear import receptors
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p.674
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Protein transport into Mitochondria and
Chloroplast
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Mitochondria and chloroplast protein import

• Signal sequences are amphipathic a helix
  consisted of positively charged and uncharged
  amino acids.
• Proteins are transported through TOM, TIM and OXA
  complexes
• ATP hydrolysis and H gradient drive
  mitochondrial and chloroplast protein import
• Most of the time, signal sequences are cleaved
  after transport.

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ATP hydrolysis and electrochemical H gradient
are used to drive protein import into mitochondria
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Signal sequences are amphipathic a helix
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Thylakoid protein targeting
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Perxisome protein targeting

• Perxisomes are different from mitochondria and
  chloroplasts.

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Peroxisome Functions

• Peroxisomes are sites for b oxidation.
• In animals, b oxidation happens in both
  mitochondria and peroxisomes.
• In yeast and plant cells, b oxidation happens in
  peroxisomes exclusively.
• Animal peroxisome is important in catalyzing the
  first reactions of plasminogens synthesis.

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plasminogen
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Plant peroxisome

• Peroxisomes in leaves are important for
  photorespiration.
• Peroxisomes in germinating seed are essential for
  converting fatty acids into sugars (glyoxysome).

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Peroxisome protein targeting

• Signal sequences are either 3 amino acids (SKL)
  sequences located at the C terminus or some
  (uncharacterized) sequences near N terminus.
• Import mechanisms are poorly understood.
• At least 23 peroxins are involved in recognition
  and docking of peroxisomal proteins.
• ATP is also required for peroxisome protein
  targeting.

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ER protein targeting

• SRP (signal-recognition particle) and SRP
  receptor guide proteins with ER signal sequence
  to ER.
• Proteins are transferred across the ER membrane
  through a translocator Sec61 complex
  co-translationally.
• Signal sequences has eight or more nonpolar amino
  acids at its center (p. 667).
• Signal sequence is removed from most soluble
  proteins after translocation.

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SRP (signal-recognition particle)
Large hydrophobic pocket lined by methionines
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Protein synthesis is paused
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Signal sequence in the growing polypeptide chain
binds to a specific site inside the pore to open
it.
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Sec61 complex
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Glycosylation

• N-linked oligosaccharide ER
• O-linked oligosaccharide Golgi (mechanism
  unknown)

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Glycosylation and protein folding

• Oligosaccharyl transferase will transfer
  oligosaccharide to the target asparagine as soon
  as that amino acid has emerged into the ER lumen
  during protein translocation.

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Nucleus
cytosol
ER lumen