Post-translational Modification Flashcards
simplest form of cleavage
The removal of methionine at the start of a newly synthesized polypeptide.
What are proproteins?
Many proteins are synthesized as inactive precursors (proproteins) that are activated under proper physiological conditions by limited proteolytic cleavage.
What are preproproteins and give an example?
Proteins synthesized with a signal peptide for targeting are called preproproteins and require further proteolytic cleavage to be functional. Example: Insulin.
What is protein methylation?
Protein methylation is a post-translational modification where methyl groups are added to proteins on nitrogens and oxygens.
What is the activated methyl donor in protein methylation?
The activated methyl donor in protein methylation is S-adenosylmethionine (SAM).
Which amino acids are most commonly methylated in proteins?
The most common methylations occur on lysine and arginine residues.
What is the most common site of acetylation in proteins?
The most common acetylations occur on lysine residues.
What is the activated acetyl donor for lysine acetyltransferases (KAT enzymes)?
The activated acetyl donor for lysine acetyltransferases (KAT enzymes) is acetyl-CoA.
What is the significance of N-terminal acetylation in proteins?
N-terminal acetylation creates a specific degradation signal for the protein.
How is a phosphate group added and removed in protein phosphorylation?
A phosphate group is added by a specific kinase and later removed by a specific phosphatase.
What role does Vitamin C play in the modification of proteins?
Vitamin C is necessary for the hydroxylation of proline and lysine by prolyl hydroxylases and lysyl hydroxylases.
Which proteins are most significantly hydroxylated?
The most significant hydroxylated proteins are collagens, which contain hydroxyproline and hydroxylysine.
Besides vitamin C, what else is required for hydroxylation of procollagen molecules?
molecular oxygen and ferrous ions
What is the function of hydroxyproline in collagen?
Hydroxyproline stabilizes the collagen triple helix by forming interstrand hydrogen bonds. Insufficiently hydroxylated collagen forms abnormal fibers, contributing to skin lesions and blood vessel fragility seen in scurvy.
List some symptoms of scurvy.
fatigue and weakness, bleeding gums, joint and muscle pain, easy bruising, slow wound healing, swollen and bleeding gums, dry, scaly skin
(a) Which blood coagulation factors require post-translational modification of glutamate residues to γ-carboxyglutamate?
(b) What enzyme catalyzes the carboxylation of glutamic acid residues?
(a) Blood coagulation factors II, VII, IX, and X.
(b) The enzyme γ-glutamyl carboxylase.
What does γ-glutamyl carboxylase require as a cosubstrate/cofactor?
Reduced vitamin K
Discuss the role of vitamin K and enzymes involved in the process of post-translational modification of glutamate residues to γ-carboxyglutamate [in relation to blood clotting factors].
◾ Vitamin K undergoes a cycle of oxidation and reduction; it starts as vitamin K hydroquinone, which is oxidized to vitamin K epoxide during the carboxylation of glutamic acid residues on specific proteins.
◾ γ-glutamyl carboxylase, which is vitamin K-dependent, adds a carboxyl group to these proteins.
◾ This modification is crucial for the proteins to bind calcium ions, necessary for their biological activity.
◾ After the carboxylation reaction, vitamin K is in its epoxide form and needs to be reduced back to its active hydroquinone form by the enzyme vitamin K epoxide reductase for the cycle to continue and for vitamin K to be reused.
Vitamin K epoxide reductase is inhibited by the drug ________.
warfarin
vitamin K epoxide reductase inhibitor used to kill rodents
bromadiolone
Which one of the following blood coagulation factors requires post-translational modification?
(a) Fibrinogen
(b) Tissue factor
(c) Proaccelerin
(d) Prothrombin
(e) Antihemophilic factor
(d) Prothrombin
Further notes:
The four clotting factors that require post-translational modification:
Factor II: Prothrombin
Factor VII: Proconvertin (or Stable Factor)
Factor IX: Christmas Factor (or Antihemophilic Factor B)
Factor X: Stuart-Prower Factor
The following are post-translational modifications, EXCEPT
(a) Proteolytic cleavage of proteins
(b) Protein methylation
(c) Polyadenylation
(d) Formation of hydroxyproline
(e) Phosphorylation of enzymes
(c) Polyadenylation
Which one of the following blood coagulation factors does not require post-translational modification?
(a) Factor II
(b) Factor VII
(c) Factor I
(d) Factor IX
(e) Factor X
(c) Factor I
Newly synthesized polypeptides in the membrane and lumen of the ER undergo the following principal modifications except ________.
(a) Formation of disulfide bonds
(b) Specific proteolytic cleavages
(c) Assembly into multimeric proteins
(d) Addition processing of carbohydrates
(e) Alternative splicing
(e) Alternative splicing
Which one of the following blood coagulation factors requires posttranslational modification?
(a) Fibrinogen
(b) Antihemophilic factor
(c) Christmas factor
(d) Proaccelerin
(e) Tissue factor
(c) Christmas factor
Which of the following statements is not true about hydroxyproline?
(a) Its formation requires Fe2+ and molecular O2
(b) It is an important constituent of mature collagen
(c) Low amounts of hydroxyproline causes scurvy
(d) Formation of hydroxyproline from proline is dependent on Vitamin C
(e) It causes skin lesions and blood-vessel fragility
(e) It causes skin lesions and blood-vessel fragility
Scurvy is caused by ________.
(a) poorly deposited collagen
(b) lower amounts of hydroxyproline
(c) lack of vitamin C
(d) all of the above
(e) none of the above
(e) all of the above
