ER Luminal Proteins and Signal Recognition

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Questions and Answers

What is the function of the signal recognition particle (SRP)?

To translate the protein

To add sugar residues to the protein

To cleave the N-terminal signal sequence

To recognise the signal sequence and arrest translation (correct)

What happens to the signal sequence after translation is resumed?

It is inserted into the ER membrane

It is released into the ER lumen

It is passed to the Golgi apparatus

It is cleaved by a protease (correct)

What is the role of oligosaccharyl transferase in protein synthesis?

To form disulphide bonds

To add sugar residues to the protein (correct)

To cleave the signal sequence

To recognise the signal sequence

What is the function of chaperone proteins in the ER lumen?

To help the protein fold correctly Signup and view all the answers

What happens to misfolded proteins in the ER lumen?

They are degraded via ERAD Signup and view all the answers

What is the purpose of the translocon in the ER membrane?

To survey the growing protein and form membrane-spanning domains Signup and view all the answers

What is the fate of the SRP after translation is resumed?

It is re-used Signup and view all the answers

Where do proteins that are damaged in the ER lumen get moved to for degradation?

The cytosol Signup and view all the answers

What is the function of ubiquitin ligase?

To attach ubiquitin to lysine residues on proteins for degradation Signup and view all the answers

What is the result of the delta 508F mutation in cystic fibrosis?

CFTR is marked for degradation via the ERAD pathway Signup and view all the answers

How does human cytomegalovirus (HCMV) evade the immune system?

By diverting MHC for degradation Signup and view all the answers

What is the role of Rab in organelle identity?

To label organelles with identity Signup and view all the answers

What happens to proteins folded and N-glycosylated in the ER?

They are transported to the Golgi Signup and view all the answers

What is the function of the M6P receptor?

To recognize and bind to M6P-modified proteins Signup and view all the answers

What is the result of defective Rabs?

Diseases arise from abnormal organelles Signup and view all the answers

What is the role of SNARE proteins?

To mediate organelle fusion Signup and view all the answers

What is the purpose of COPI vesicles?

To transport proteins from the Golgi to the ER Signup and view all the answers

What is the purpose of enzyme replacement therapy (ERT)?

To replace missing lysosomal enzymes Signup and view all the answers

Study Notes

ER Protein Synthesis and Modification

ER luminal proteins have a hydrophobic signal sequence (more than 8 contiguous hydrophobic residues) at the N-terminal, while integral membrane proteins have this sequence internally.
The signal sequence is recognized by the signal recognition particle (SRP) as soon as it is translated, leading to translation arrest.
The SRP-nascent peptide chain associates with the SRP receptor on the ER membrane, and then with a translocon (ER membrane channel) to check the signal sequence.
The nascent peptide is inserted into the translocon in the appropriate orientation, which is crucial as it cannot be altered later.

Protein Modification in the ER Lumen

As the growing peptide emerges into the ER lumen, it is scrutinized by enzymes such as protease, which cleaves any N-terminal signal sequence.
Oligosaccharyl transferase identifies asparagine residues and adds pre-assembled sugar residues in a process known as N-linked glycosylation.
Chaperone proteins, such as BiP, help the growing peptide fold into its correct shape.

ER Quality Control and Degradation

Misfolded ER proteins are removed through the ER-associated degradation (ERAD) pathway, which involves ubiquitin ligase and the attachment of ubiquitin to lysine residues.
More than 30% of all ER proteins are marked for degradation.
Defects in the ERAD pathway can lead to diseases, such as cystic fibrosis and Parkinson's disease.

Protein Trafficking from the ER

Proteins are packed into vesicles and transported to other organelles, with identity labels such as Rab and lipids.
Rab is a small G-protein that is active when bound to GTP and inactive when bound to GDP, and plays a crucial role in organelle recognition.
Defective Rabs can cause diseases, such as Charcot-Marie-Tooth disease and legionnaire's disease.

Golgi Apparatus and Protein Modification

Proteins folded and N-glycosylated in the ER are collected into COPII vesicles to move to the cis Golgi.
Within the Golgi, sugar structures of most proteins are trimmed and modified, and proteins directed for lysosomes are marked with mannose-6-phosphate (M6P).

Lysosomal Function and Disease

Soluble proteins destined for lysosomes are recognized by the M6P receptor, which binds to the M6P modification.
Many enzymes are uniquely expressed in lysosomes, and genetic differences in these enzymes can lead to lysosomal storage diseases (LSDs).
Enzyme replacement therapy (ERT) is a treatment for LSDs, which involves administering M6P-modified forms of missing enzymes.

Endocytosis and LDL Receptor

Low density lipoprotein (LDL) receptors bind to the ApoB-100 component of LDL and are internalized through clathrin-coated pits.
In the acidic lumen of endosomes, LDL dissociates from its receptor, and is then passed to lysosomes for degradation.
The LDL receptor is recycled to the plasma membrane, making up to 100 trips before being degraded.

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Description

This quiz covers the structure and function of ER luminal proteins, including signal sequences and the role of the signal recognition particle (SRP) in protein translation and translocation.