Please enable JavaScript.
Coggle requires JavaScript to display documents.
intracellular proteolysis - Coggle Diagram
intracellular proteolysis
regulation of protein function
damaging protein (negative regulation)
oxidation
deamination
glycation
nitrosylation
high [salt] dissociates protein complexes
unfolded proteins can be sticky and aggregate other proteins
mutations
transcriptional/translational error
normal regulation (+-ve)
phosphorylation
active site and allosteric regulators
protein degradation
Turnover
experimental observations
turnover rate increases in starvation
different proteins have different turnover rates:
proteins that are
metabolic control points
have
shorter
half lives
MCP = protein responsible for regulating a pathway
characteristics
continuous process
ATP dependent
multiple degradation pathways
N terminal rule
the N terminus is important in selecting proteins for degradation
found through mutating the N terminus of a protein to each of the other different amino acids
it was found that degradation selection is a fairly conserved pathway
zymogens
inactive precursors
protein degradation
(Cont.)
classes of proteases
serine
how does it function?
in active site, there is a
catalytic triad
series of 3 amino acids (Asp, His,
Ser
) when in the specific arrangement in space become very reactive;
due to the negative Asp, and it bonding His, and the arrangement in space... the
Ser
has an
alkoxide ion
, which is hella reactive
cysteine
aspartic
metalloprotease
major families of intracellular proteases
caspases
aspartate protease (cysteine dependent)
apoptosis protein
regulated by pro-enzyme activation
cathepsins
cysteine protease
lysosomal protease
optimal pH low
calpains
cysteine protease
Ca dependent
restricted specificity
pro protein convertases
serine protease
Ca dependent
cleaves these kinda proteins
hormones
growth factors
neuropeptides
proteasome
only example
of a
threonine protease
ubiquitin dependent
threonine
selecting protein for degradation
lysosomes
cathepsins are the major protease within lysosomes
delivery mechanisms to lysosome
endocytosis:
as pH drops, hydrolysis occurs
late endosome is a precursor to lysosome
autophagy
means
self eating
things engulfed by ER derived vesicle
autophagosome directed to lysosome
phagocytosis
chaperone mediated autophagy
target proteins with a specific signal sequence bind to chaperone proteins, which escort them to the lysosome
transport of acid hydrolases to lysosome
enzymes must have a M6P tag
M6P tagged enzymes bind the M6P receptor within trans golgi
transported to the early endosome
pH drop dissociates protein from its receptor
eventually vesicle develops into lysosome
this is added in golgi by:
there is a mannose residue on these enzymes (look at onenote)
enzyme attaches GlcNAc phosphotransferase.... itself binding UDP-GlcNAc
GlcNAc-P is added to mannose residue (by P)
GlcNAc removed