Protein Modification And Transport

Question 1

Does the protein remain folded or unfolded during nuclear transport?

Answer 1

FOLDED

Question 2

What is the nature of the NLS signal on nuclear proteins?

Answer 2

• BASIC

- Contains Lys and Arg residues

Question 3

Are mitochondrial proteins folded or unfolded when transported into the mitochondria?

Answer 3

PARTIALLY UNFOLDED held by chaperone

Question 4

What proteins are involved in mitochondrial protein transport?

Answer 4

• MSF
• TOM and TIM transmembrane receptors
• Matrix processing protease
• Chaperone

Question 5

What is the nature of the targeting sequence for mitochondrial protein transport?

Answer 5

AMPHIPATHIC signal sequence on N terminus

Question 6

What is retrograde transport?

Answer 6

Transport of KDEL-receptor bound ER resident protein from cis Golgi to ER

Question 7

What is anterograde transport?

Answer 7

Transport of soluble resident proteins of ER to cis Golgi

Question 8

What is the nature of the signal which is present on soluble resident proteins of the ER?

Answer 8

KDEL sequence on C terminus (Lys-Asp-Glu-Leu)

Question 9

What is the role of the signal recognition protein SRP in the transport of proteins into the ER cisternae?

Answer 9

• Detects signal sequence on N terminus of protein
• Inhibits translation guides target protein and ribosome to the ER membrane
• Binds to SRP receptor which opens protein translocon channel and protein is fed from ribosome through to ER cisternae
• Dissociation of the SRP from the receptor requires GTP hydrolysis

Question 10

What is significant about the pH of the Golgi which allows retrograde transport of ER resident proteins to occur?

Answer 10

• Lower pH in Golgi compared to ER
• KDEL receptor has a higher affinity for KDEL sequence so will bind
• KDEL receptor-protein complex is recognised and transported back to ER

Question 11

What is the importance of glycosylation of proteins?

Answer 11

• Ensures correct folding of protein
• Protein stability (extends half life)
• Cell adhesion and communication

Question 12

Where does glycosylation of proteins occur?

Answer 12

• POST TRANSLATIONAL
• N linked glycosylation occurs in ER
• O linked glycosylation occurs in Golgi

Question 13

How are lysosomal proteins identified and transported to lysosomes?

Answer 13

• Post translational modification of mannose sugar in Golgi to form MANNOSE-6-PHOSPHATE by the enzymes N ACTEYL GLUCOSAMINE PHOSPHOTRANSFERASE and PHOSPHODIESTERASE
• M6P receptor recognises patch of phosphorylated mannose sugars and instigates RECEPTOR MEDIATED TRANSPORT of the protein to the lysosome
• Low pH of the lysosome causes the M6P receptor to dissociate and mannose sugar is dephosphorylated by PHOSPHATASE enzymes in lysosome

Question 14

What is I cell disease?

Answer 14

• Deficiency in N acetyl glucosamine phosphotransferase
• Lysosomal enzymes cannot be modified in Golgi and transported to lysosomes
• Lysosomes become bloated with undigested material

Question 15

What is meant by constitutive secretion?

Answer 15

• NOT REGULATED

- Occurs constantly

Question 16

Describe the process of transport of a protein into the nucleus

Answer 16

• Nuclear Localisation Signal NLS is located on surface of folded protein (variable positions)
• NLS recognised by Importin which binds to it and facilitates transport into nucleus through nuclear pore
• RanGTP binds to Importin within nucleus causing a conformational change which causes Importin to displace cargo
• RanGTP and Importin are recycled in the cytoplasm (requires GTP hydrolysis)