S8) Post-translational Modifications Flashcards
Describe the basis for post-translational modification
- All proteins adopt a unique 3D structure to become active
- Some proteins need additional processing after translation to adopt this structure
Identify and describe 2 forms of post-translational modifications that can occur
- Proteolytic cleavage – breaking peptide bonds to remove part of the protein
- Chemical modification – addition of functional groups to amino acid residues
What are the 2 different post-translational destinations for proteins?
- Proteins destined for the cytosol or posttranslational import into organelles
- Proteins destined for a membrane or secretory pathway via co-translational insertion
Where are proteins destined for the cytosol /posttranslational import into organelles synthesised?
Synthesised on free ribosomes
Where are proteins destined for a membrane / secretory pathway via co-translational insertion synthesised?
Synthesised on ribosomes bound to rER
What are the 4 requirements for protein sorting?
- A signal (address), intrinsic to the protein
- A receptor that recognises the signal and which directs it to the correct membrane
- A translocation machinery
- Energy to transfer the protein to its new place
Identify 3 organelles which are targeted by proteins
- Peroxisomes
- Mitochondria
- Nucleus
Identify 3 types of proteins which are targeted for secretion
- Extracellular proteins
- Membrane proteins
- Vesicular proteins (lysosomes, endosomes etc)
Identify the 2 types of secretion from cells
What is consitutive secretion?
Constitutive secretion is the constant flow of extracellular proteins out of the cell e.g. collagen is a secreted and modified protein
What are the 3 forms of regulated secretion?
- Endocrine – secreting hormones
- Exocrine – secreting digestive juices
- Neurocrine – secreting neurotransmitters
In 7 steps, explain how proteins are targeted to the ER/secretory pathway (co-translational transport)
⇒ Protein synthesis on bound ribosomes
⇒ Co-translational transport of proteins into or across ER membrane
⇒ Budding and fusion of ER-to-Golgi vesicles to form cis-Golgi
⇒ Cisternal progression
⇒ Consitutive secretion / Regulated secretion
⇒ Sorting into Lysosomes
⇒ Endocytosis
Identify 6 functions of the ER
- Insertion of proteins into membranes
- Specific proteolytic cleavage
- Glycosylation
- Formation of S-S bonds
- Proper folding of proteins
- Assembly of multi-subunit proteins
What is N-linked glycosylation and where does it occur?
- N-linked glycosyation is a reaction involving an amino group where sugars are added on an asparagine side chain
- Occurs in ER
What does glycosylation of proteins do?
- Folds protein correctly
- Stabilises protein
- Facilitates interactions with other molecules
What can deficiencies in N-linked glycosylation lead to?
Severe inherited human diseases - congenital disorders of glycosylation
What is a disulphide bond?
A disulphide bond is a linkage derived by the coupling of two thiol groups
What happens if there are protein folding problems?
- Protein may be trapped in mis-folded conformation
- Protein contains mutation resulting in mis-folding
- Protein may be incorrectly associated with other sub-units
Identify 3 ER chaperone proteins that attempt to correct misfolding
- BiP: “Binding Immunoglobulin Protein”
- Calnexin
- Calreticulin
How do ER chaperone proteins attempt to correct protein misfolding?
- Retain unfolded proteins in the ER
- Act as sensors to “monitor” extent of protein mis-folding
- Mediate increased transcription of chaperones
- Mediate reduction in translation
What happens if protein misfolding cannot be corrected?
- Protein may be returned to cytosol for degradation
- Protein may accumulate to toxic levels in the ER causing disease
What is O-linked glycolisation and where does it occur?
- O-linked glycosylation is a process important in proteoglycans, involving the attachment of sugar to -OH group of serine/threonine
- Occurs in Golgi apparatus
Insulin is a protein that undergoes post-translation modifications.
Describe the processing of preproinsulin
- Signal peptide removed on entry into ER
- Disulphide bonds formed in ER
- Removal of C chain in Golgi
Proteins may be delivered to the plasma membrane via the regulated or secretory constitutive pathway.
Identify 4 proteins delivered via the constitutive secretory pathway
- Immunoglobulins
- Albumin
- Prohormones
- Collagen
Proteins may be delivered to the plasma membrane via the constitutive or regulated secretory pathway.
Identify 3 proteins delivered via the regulated secretory pathway
- Insulin
- Glucagon
- Trypsin
