Protein Targeting Flashcards Preview

ESA 1 - MCBG > Protein Targeting > Flashcards

Flashcards in Protein Targeting Deck (12)
Loading flashcards...
1
Q

Which proteins are synthesised on free ribosomes and which on rER ribosomes?

A
  • Free ribosomes: proteins remaining in cytosol or that are post-translationally imported into organelles.
  • rER ribosomes: proteins destined for secretion, PM or lysosomes.
2
Q

What are the 4 requirements for protein sorting?

A
  1. Signal (intrinsic to protein, except for cytosolic proteins)
  2. Receptor: recognises signal and directs it to correct membrane.
  3. Translocation machinery
  4. Energy
3
Q

What are the requirements for peroxisomal protein targeting?

A
  1. Peroxisome targeting sequence (PTS). Usually present on C-terminus of protein.
  2. PTS receptor Pex5.
  3. Translocon made up of 13 Pex proteins.
  4. ATP hydrolysis for recycling of PTS receptor.
4
Q

Describe the process of peroxisomal targeting.

A
  1. PTS receptor (Pex5) binds to PTS in cytosol.
  2. PTS receptor integrates into translocon to open it - dissociates from PTS.
  3. Folded protein enters PO matrix.
  4. PTS receptor returns to cytosol via ATP hydrolysis.
5
Q

What is the result of faulty PO targeting?

A

Peroxisome biogenesis disorders. E.g.

  • ZELLWEGER SYNDROME: mutation in any of 12 PEX genes (inc. Pex5)… no PO protein targeting… VLFCA accumulation… neurone development impairment.
  • RHIZOMELIC CHONDRODYSPLASIA PUNCTATE: mutation of Pex7 leads to skeletal abnormalities.
6
Q

What are the 2 types of cellular secretion of proteins and give examples of each.

A
  1. Constitutive secretion
    • collagen secretion from fibroblasts
    • albumin secretion from hepatocytes
  2. Regulated secretion
    • endocrine cells secreting hormones
    • exocrine cells secreting digestive juices
    • neurocrine cells secreting NTs
7
Q

Describe the process of protein targeting to the ER.

A

Involves co-translational protein translocation.

  1. N-terminal signal sequence on protein being translated recognised by Signal Recognition Particle (SRP).
  2. SRP binds to signal sequence and to ribosome.
  3. SRP binds to SRP receptor in ER membrane. GTP for GDP exchange on SRP and SRP R opens translocon. SRP dissociates.
  4. Polypeptide is translated through the translocon.
  5. Signal peptidase cleaves signal sequence as polypeptide enters ER lumen.
  6. Polypeptide is released into lumen.
8
Q

What is type I ER membrane protein synthesis? What does this require?

A
  • Insertion of polypeptide destined for PM or internal membrane of secretory pathway into ER membrane.
  • Stop-transfer anchor sequence.
9
Q

Describe the requirements for targeting of proteins retained in the ER.

A
  • KDEL or KKXX signal sequence at C-terminus.
  • KDEL receptor.
  • Protein remains folded during translocation and signal sequence is retained.
  • No energy requires except from GTP hydrolysis required for vesicle budding.
10
Q

Describe the components of protein targeting to lysosomes. What does the signal sequence involve?

A
  • Signal sequence = N-linked glycosylation of asparagine residues - adds on M6P.
  • Recognised by M6P receptor on membrane of Golgi trans face.
  • M6P is cleaved by acidic pH of lysosomes.
  • Protein is translocated folded.
  • Energy is required for vesicle movement and hydrogen pump (ATP hydrolysis).
11
Q

Describe the components of protein targeting to mitochondria.

A
  • Signal sequence is bi-partite: matrix-specific sequence (cleaved in matrix) and region-specific targeting sequence. Located in N-terminus.
  • Signal sequence cleaved by signal peptidase.
  • Protein is translocated unfolded.
  • Many specialised proteins involved: SRP, SRP receptor, chaperone proteins (MSF) or cytosolic Hsc70, TOMs, TIMs.
  • Requires ATP hydrolysis.
12
Q

Describe the components of protein targeting to the nucleus.

A
  • Signal sequence = internal Nuclear Localisation Signal (monopartite or bipartite).
  • NLS is retained so that protein can re-enter nucleus after mitotic envelope degradation.
  • Protein is translocated when folded. Involves alpha and beta importin receptors, nuclear pore, RanGTP, RanGAP, etc.
  • GTP hydrolysis is required for recycling of importin (RanGTP to RanGDP).