04.12.19
L8– Cells as the fundamental unit in biology
Keywords:
Chaperons (keep in an unfolded state whilst being processed)
Lecture:
Turnover of proteins
o Fold independently, folding (w/chaperons), misfold (non-functional use proteasome
when single protein), protein aggregates (autophagy)
o 1 error/10 proteins
Monitoring protein quality
o Unfolded protein + chaperon (Hsp60) = folding independently w/o other proteins
HS = heat shock (maintain folding of proteins in heat stress)
o Hydrolyzation of ATP and covered by a GroES cap to fold protein
o Hydrolyzation of ATP to release protein
Disease and protein turnover (single cell analysis)
o Increased misfolding aggregation (more recycling) = Parkinson’s via α-synuclein
o Increased protein production = Alzheimer’s via Aβ peptide
o Increased degradation = cystic fibrosis via CFTR protein
Proteasome (dustbin)
o 80-90% of breakdown
o Tagged for self/non self and for destruction in MXC proteins
o S = Svedberg units (measure density of the structures)
o Synth
Jak (just another kinase) regs stat2 to then synth DNA for protein synth
o 2 forms of the proteasome (switch between w/ATP)
20s version ( w/β subunits)
26s version (binds w/19s subunits)
o Stack to form barrel and caps (19s) interacts w/ends and digest different proteins
dependent upon cap (can interact to bind to other proteins)
Chaperone proteins help guide the protein into the proteasome
Ubiquitin = small proteins (76 AA) that modify protein complexes
Stop ubiquitination via the methylation/acetylation of the lysine AA
Polyubiquitin (linear/branched) can occur on different lysine AAs on
the chain
o (Multi-)Monoubiquitinylation = protein
identification/localization/modulation of activity
o Branched ubiquitin chains = unknown
Polyubiquitination = needed to be broken down (eg p53 degradation) to
stop cancer
Ubiquitin subunits that were bound to protein (eg p53 recycled)
Acetylation occurs on lysine residues that are also used for ubiquitylation
(therefore cannot be destroyed) via E1-3 enzymes
E3 = ubiquitin ligase to bind ubiquitin to a protein
o E3 and E2 are in a complex
Signal to send protein to proteasome
L8– Cells as the fundamental unit in biology
Keywords:
Chaperons (keep in an unfolded state whilst being processed)
Lecture:
Turnover of proteins
o Fold independently, folding (w/chaperons), misfold (non-functional use proteasome
when single protein), protein aggregates (autophagy)
o 1 error/10 proteins
Monitoring protein quality
o Unfolded protein + chaperon (Hsp60) = folding independently w/o other proteins
HS = heat shock (maintain folding of proteins in heat stress)
o Hydrolyzation of ATP and covered by a GroES cap to fold protein
o Hydrolyzation of ATP to release protein
Disease and protein turnover (single cell analysis)
o Increased misfolding aggregation (more recycling) = Parkinson’s via α-synuclein
o Increased protein production = Alzheimer’s via Aβ peptide
o Increased degradation = cystic fibrosis via CFTR protein
Proteasome (dustbin)
o 80-90% of breakdown
o Tagged for self/non self and for destruction in MXC proteins
o S = Svedberg units (measure density of the structures)
o Synth
Jak (just another kinase) regs stat2 to then synth DNA for protein synth
o 2 forms of the proteasome (switch between w/ATP)
20s version ( w/β subunits)
26s version (binds w/19s subunits)
o Stack to form barrel and caps (19s) interacts w/ends and digest different proteins
dependent upon cap (can interact to bind to other proteins)
Chaperone proteins help guide the protein into the proteasome
Ubiquitin = small proteins (76 AA) that modify protein complexes
Stop ubiquitination via the methylation/acetylation of the lysine AA
Polyubiquitin (linear/branched) can occur on different lysine AAs on
the chain
o (Multi-)Monoubiquitinylation = protein
identification/localization/modulation of activity
o Branched ubiquitin chains = unknown
Polyubiquitination = needed to be broken down (eg p53 degradation) to
stop cancer
Ubiquitin subunits that were bound to protein (eg p53 recycled)
Acetylation occurs on lysine residues that are also used for ubiquitylation
(therefore cannot be destroyed) via E1-3 enzymes
E3 = ubiquitin ligase to bind ubiquitin to a protein
o E3 and E2 are in a complex
Signal to send protein to proteasome
