Case 6: Where do the proteins end up? BBS1001 2023/2024
22 september 2023
Keywords
- Protein destination
- Protein transport
- Pathways
- Protein deficiencies
- Gaucher’s disease
- I-cell disease
- Proper function
Problem statement
Proper protein transport and destination.
Learning goals
1. How are proteins folded after translation? (what Is the function of chaperones in
protein folding)
2. What are post-translational modifications? Protein folding, Glycosylation,
Proteolysis, Hydroxylation, Disulfide bridge formation, Phosphorylation.
3. How are proteins directed to their final position in the cell?
o Which steps are important?
o Which organelles and helper proteins (chaperones) are involved?
o Which pathways are important.
4. What happens if proteins are misfolded?
5. What is Gaucher’s disease/I-cell disease?
o How Is protein transport affected in these two diseases?
o What are the consequences of malfunctioning protein transport in these
diseases?
Gaucher’s disease:
- Lysosomal storage disease
- Rare inherent disorder
- Deficiency of glucocerebrosidase produced in ER transported by Golgi body to
the lysosome catalyzes breakdown of its main substrate glucocerebroside
(glucose + ceramide)
- Glucocerebroside essential for vital cellular activities.
- Deficiency of glucocerebrosidase lead to the lysosomal accumulation of
glucocerebroside.
- Macrophages laden with excess glucocerebroside = Gaucher cells
- Accumulation of Gaucher cell in the liver, spleen and bone marrow gives rise to the
typical clinical manifestations of Gaucher’s disease.
- Gaucher cells secrete cytokines which can contribute to the signs and symptoms
of disease.
, Case 6: Where do the proteins end up?
1. How are proteins folded after translation? Function chaperones.
The folding of a protein involves four stages:
- Primary structure: refers to the linear sequence of amino acid residues in the
polypeptide chain.
- Secondary structure: is generated by formation of hydrogen bonds between atoms
in the polypeptide backbone, which folds the chains into either alpha helices or beta-
sheets.
o Alpha helix fold
o Beta-pleated sheet
- Tertiary structure: is formed by the folding of the secondary structure sheets or
helices into one another. The tertiary structure of protein is the geometric shape of
the protein. It usually has a polypeptide chain as a backbone, with one or more
secondary structures. The tertiary structure is determined by the interactions and
bonding of the amino acid side chains (R-group) in the protein.
Influence tertiary structure:
o Hydrophilic R-group hang out on the outside.
o Hydrophobic R-group hang out in the inside.
o Ionic bonds
o Disulfide bonds (disulfide bridges)
o Hydrogen bonds
o Van der Waals interactions
- Quaternary structure: results from folded amino-acid chains in tertiary structures
interacting further with each other to give rise to a
functional protein such as hemoglobin or DNA
polymerase.
Factors affecting protein folding.
Protein folding is a very sensitive process that is influenced by
several external factors including electric and magnetic fields,
temperature, pH, chemicals, space limitation and molecular
crowding. These factors influence the ability of proteins to fold
into their correct functional forms.
Extreme temperatures affect the stability of proteins and cause
them to unfold or denature. Similarly, extreme pH, mechanical
forces and chemical denatures can denature proteins. During
denaturation, proteins lose their tertiary and secondary
structures and become a random coil. Although denaturation is
not always reversible, some proteins can re-fold under certain
conditions.
Chaperones are a functionally related group of proteins
assisting protein folding in the cell under psychological and
stress conditions.
Chaperones binds after the translation.
U can find chaperones in the RER.
22 september 2023
Keywords
- Protein destination
- Protein transport
- Pathways
- Protein deficiencies
- Gaucher’s disease
- I-cell disease
- Proper function
Problem statement
Proper protein transport and destination.
Learning goals
1. How are proteins folded after translation? (what Is the function of chaperones in
protein folding)
2. What are post-translational modifications? Protein folding, Glycosylation,
Proteolysis, Hydroxylation, Disulfide bridge formation, Phosphorylation.
3. How are proteins directed to their final position in the cell?
o Which steps are important?
o Which organelles and helper proteins (chaperones) are involved?
o Which pathways are important.
4. What happens if proteins are misfolded?
5. What is Gaucher’s disease/I-cell disease?
o How Is protein transport affected in these two diseases?
o What are the consequences of malfunctioning protein transport in these
diseases?
Gaucher’s disease:
- Lysosomal storage disease
- Rare inherent disorder
- Deficiency of glucocerebrosidase produced in ER transported by Golgi body to
the lysosome catalyzes breakdown of its main substrate glucocerebroside
(glucose + ceramide)
- Glucocerebroside essential for vital cellular activities.
- Deficiency of glucocerebrosidase lead to the lysosomal accumulation of
glucocerebroside.
- Macrophages laden with excess glucocerebroside = Gaucher cells
- Accumulation of Gaucher cell in the liver, spleen and bone marrow gives rise to the
typical clinical manifestations of Gaucher’s disease.
- Gaucher cells secrete cytokines which can contribute to the signs and symptoms
of disease.
, Case 6: Where do the proteins end up?
1. How are proteins folded after translation? Function chaperones.
The folding of a protein involves four stages:
- Primary structure: refers to the linear sequence of amino acid residues in the
polypeptide chain.
- Secondary structure: is generated by formation of hydrogen bonds between atoms
in the polypeptide backbone, which folds the chains into either alpha helices or beta-
sheets.
o Alpha helix fold
o Beta-pleated sheet
- Tertiary structure: is formed by the folding of the secondary structure sheets or
helices into one another. The tertiary structure of protein is the geometric shape of
the protein. It usually has a polypeptide chain as a backbone, with one or more
secondary structures. The tertiary structure is determined by the interactions and
bonding of the amino acid side chains (R-group) in the protein.
Influence tertiary structure:
o Hydrophilic R-group hang out on the outside.
o Hydrophobic R-group hang out in the inside.
o Ionic bonds
o Disulfide bonds (disulfide bridges)
o Hydrogen bonds
o Van der Waals interactions
- Quaternary structure: results from folded amino-acid chains in tertiary structures
interacting further with each other to give rise to a
functional protein such as hemoglobin or DNA
polymerase.
Factors affecting protein folding.
Protein folding is a very sensitive process that is influenced by
several external factors including electric and magnetic fields,
temperature, pH, chemicals, space limitation and molecular
crowding. These factors influence the ability of proteins to fold
into their correct functional forms.
Extreme temperatures affect the stability of proteins and cause
them to unfold or denature. Similarly, extreme pH, mechanical
forces and chemical denatures can denature proteins. During
denaturation, proteins lose their tertiary and secondary
structures and become a random coil. Although denaturation is
not always reversible, some proteins can re-fold under certain
conditions.
Chaperones are a functionally related group of proteins
assisting protein folding in the cell under psychological and
stress conditions.
Chaperones binds after the translation.
U can find chaperones in the RER.
