Sugars part 2

  1. In eukaryotic cells through a process known as __, sugars are used to monitor the quality of protein folding in the ER
    N-glycosylation

    (Sugars can also eliminate improperly folded proteins in the ER)
  2. a protein that contains covalently linked sugars
    Glycoprotein
  3. Glycosylation motif
    Short stretch of amino acid within a protein that is to be glycosylated: NXS/T. (The side chain of N gets glycosylated.)

    • N = Asparagine
    • X = any amino acid except Proline
    • 3rd position = Serine or Threonine
  4. What is the functional significance of N-linked glycosylation?
    Guides & monitors proteins through distinct stages of protein folding in the ER
  5. What is the probability of finding ONE glycosylation motif in a protein?
    [ (1N/20) x (19X/20) x (2ST/20) ] x 100% = 0.475%

    This means at random there is less than half a % chance of finding a glycosylation motif within any given protein. There’s an even lower probability of finding more than 1 glycosylation motif
  6. all sugars on an N-linked Glycan structure
    • 3 Glucose (Glc)
    • 9 Mannose (Man)
    • 2 N-acetylglucosamine (GlcNAc)
    • = 14 total

    (See slide #16. Need to know all structures)
  7. ER-specific enzymes
    • Glucosyltransferase (UGGT): adds glucose
    • Glucosidase: removes glucose
    • Mannosidase: removes mannose
  8. Protein channel that allows passing of newly formed polypeptides
    Sec61

    (See slide #17)
  9. chaperone complex that helps to fold proteins inside the ER together with ERP57
    Calnexin-calreticulin
  10. ER lipid that holds onto sugars prior to transferring it to protein
    Dolichol (uses the help of an enzyme called OST to transfer sugars)
  11. What is ERAD & when does this take place?
    • collective terms used for ER associated degradation;
    • takes place when secretory proteins fail to fold properly & are destined to be degraded
  12. Enzyme whose function is to form disulfide bonds within secretory proteins within the ER
    ERP57
  13. EDEM
    ER protein degradation signal enhancing mannosidase

    (A mannosidase removes Mannose)
  14. Golgi-specific sugars & enzymes
    Sugars: FGSN (fucose, galactose, sialic acid, GlcNAc)

    Enzymes: ALL transferase enzymes responsible for transferring sugars onto the protein. Sugar name + transferase. Ex. Sialyl transferase is an enzyme responsible for adding sialic acid.
  15. Summary of protein folding cycle in the ER (properly folded pathway)
    (See slide #17 & 18) An SRP (signal recognition particle protein) sticks to a ribosome which then allows the ribosome to dock onto the SRP receptor on the ER. Polypeptide enters the ER through the Sec61 channel. Dolichol is holding onto the glycan (sugar molecule). OST helps Dolichol transfer the glycan onto the polypeptide. At this moment the glycan has 3 Glucose molecules. Glycosidase removes 2 glucose molecules. Calnexin-calreticulin along with ERP57 start folding the protein. Another glycosidase then removes the last glucose. Mannosidase then removes 1 mannose. Protein is now properly folded & leaves the ER to enter the Golgi apparatus
  16. If there are 3 glucose present at the edge of the glycan, that means __
    the protein just entered the ER

    (See slide #18)
  17. If there is only 1 glucose present at the edge of the glycan, that means __
    the protein is ready to enter the folding pathway

    (See slide #18)
  18. If there are no glucose present at the edge of the glycan AND exactly 1 mannose is removed, this means __
    the protein is folded & can leave the ER

    (See slide #18)
  19. If there are no glucose present at the edge of the glycan AND a lot/some of mannoses are removed, this means __
    the protein did not fold properly & is degraded through the ubiquitin-proteasome pathway

    (See slide #18)
Author
sophathida
ID
350964
Card Set
Sugars part 2
Description
N-glycosylation
Updated