CSB349H1 Lecture Notes - Lecture 13: Myristoylation, Palmitoylation, Signal Peptide
14 May 2018
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Lecture 13(b): Translational & Post-Translational Regulation
Chaperone Proteins:
• Chaperone proteins interact with the translated amino-acid
sequence while the ribosome is still translating the mRNA transcript
o Chaperone proteins have several functions:
§ Help proteins fold properly to generate the functional protein
§ Repair misfolded proteins
§ Send aggregated proteins for degredation
ð Chaperone proteins were initially termed as heat-shock proteins:
o Proteins highly induced upon stress (heat treatment); denature & lose confirmation
Post–Translational Control:
• Three major ways to control protein activity:
a. Change enzyme activity (structural/biochemical)
b. Change subcellular localization
c. Change protein stability
• Post-translation control is done via two mechanisms:
1) Covalent Modifications:
§ Phosphorylation, ubiquitination, acetylation…
2) Protein-Protein Interactions:
§ Signal peptide and other linear motifs
§ Modular signaling domains (i.e. auto-inhibitory domain; ligand activate it)
Control – Phosphorylation:
• Kinase (phosphorylating) or phosphatase (removing phosphate) can lead to the activation or
the inactivation of a protein
Kinases:
• Most kinases do not function alone – they are often involved in a large protein family
o Many protein kinases require post-translational modifications to be
activated (i.e. MAPKKK => MAPKK => MAPK => Target [TF])
§ Cascade allows for diversity; there are more MAPKKK than
MAPK – therefore, several triggers are capable of activating the
cascade through different upstream kinases, however the
downstream kinase is the same
Control – Palmitoylation & Myristoylation:
• Both function to add fatty acids to target proteins after their translation – different
fatty acids are added by each (differ in C length)
o Attaching the fatty acid will help guide the protein to a membrane
ð Similar function, but there is a phenomenon: myristoylation molecular switch:
o Inactive protein becomes active (i.e. ligand binding) and upon activation it will expose
the fatty acid residue and then capable of being guided to its target membrane
Document Summary
Lecture 13(b): translational & post-translational regulation: chaperone proteins interact with the translated amino-acid sequence while the ribosome is still translating the mrna transcript, chaperone proteins have several functions: Help proteins fold properly to generate the functional protein. Chaperone proteins were initially termed as heat-shock proteins: proteins highly induced upon stress (heat treatment); denature & lose confirmation. Post translational control: three major ways to control protein activity, change enzyme activity (structural/biochemical, change subcellular localization, change protein stability, post-translation control is done via two mechanisms, covalent modifications: Modular signaling domains (i. e. auto-inhibitory domain; ligand activate it) Control phosphorylation: kinase (phosphorylating) or phosphatase (removing phosphate) can lead to the activation or the inactivation of a protein. Kinases: most kinases do not function alone they are often involved in a large protein family, many protein kinases require post-translational modifications to be activated (i. e. mapkkk => mapkk => mapk => target [tf]) Cascade allows for diversity; there are more mapkkk than.
