The ubiquitin-proteasome mediated protein degradation pathway | Ubiquitin ligase | Proteasome
Summary
TLDRThis video script explains the ubiquitin proteasome pathway, a cellular system crucial for protein degradation. It involves ubiquitin, a small protein that tags proteins for degradation, and the proteasome, a complex that breaks down these tagged proteins. The process is likened to a sniper scenario, where ubiquitin enzymes (E1, E2, E3) mark proteins for destruction. The script also discusses the clinical relevance of this pathway, including its association with cancer, neurodegenerative diseases, and infectious diseases.
Takeaways
- 🔍 The ubiquitin proteasome pathway is critical for cellular homeostasis by degrading misfolded, damaged, and non-functional proteins.
- 🏷 Ubiquitin is a small protein that acts as a 'degradation tag' for proteins targeted for degradation.
- 🔪 The proteasome is a large complex that functions like a 'shredding machine', breaking down the tagged proteins.
- 🎯 The pathway involves a coordinated effort between E1, E2, and E3 enzymes to mark proteins for degradation.
- 🤝 E3 enzymes, or ubiquitin ligases, are particularly important as they facilitate the transfer of ubiquitin to the target protein.
- 🔗 Polyubiquitination is the key mark for protein degradation, unlike monoubiquitination which is a modification and not necessarily linked to degradation.
- 🧬 The proteasome consists of a 19S regulatory particle for recognition and unfolding, and a core particle that degrades the protein.
- 🔄 The process involves recognition of the polyubiquitinated protein by the proteasome cap, unfolding, and translocation to the catalytic core for degradation.
- 🏥 Clinically, the ubiquitin proteasome pathway is significant in diseases like cancer and neurodegenerative disorders such as Alzheimer's and Parkinson's.
- 🦠 In infectious diseases, some pathogens inhibit the proteasome pathway to avoid being recognized and presented by MHC molecules.
Q & A
What is the ubiquitin proteasome pathway?
-The ubiquitin proteasome pathway is a cellular system responsible for protein degradation, particularly targeting misfolded, damaged, or non-functional proteins to maintain cellular homeostasis.
Why is the ubiquitin proteasome pathway important for cells?
-It is crucial for maintaining cellular homeostasis by ensuring the degradation of misfolded, damaged, or non-functional proteins, thus functioning as a quality control mechanism.
What is the role of ubiquitin in the pathway?
-Ubiquitin is a small protein that tags proteins for degradation, acting as a 'degradation tag' for the proteasome to recognize and degrade.
How does the proteasome function in the pathway?
-The proteasome is a large proteolytic complex that degrades proteins marked by ubiquitin, functioning like a 'shredding machine' for proteins.
What are the two main components of the ubiquitin proteasome pathway?
-The two main components are ubiquitin, which tags proteins for degradation, and the proteasome, which degrades the tagged proteins.
What are the different enzymes involved in the ubiquitination process?
-The enzymes involved are E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugation enzyme), and E3 (ubiquitin ligase), which work together to tag proteins for degradation.
How does the E3 enzyme contribute to the ubiquitination process?
-E3 facilitates the transfer of ubiquitin from E2 to the lysine residues of the target protein, effectively flagging it for destruction by the proteasome.
What is the difference between polyubiquitination and monoubiquitination?
-Polyubiquitination is a tag for protein degradation, where the protein is marked for several rounds of ubiquitination. Monoubiquitination, on the other hand, is a protein modification that does not necessarily lead to degradation.
What are the components of the proteasome and their functions?
-The proteasome consists of a 19S regulatory particle for recognition and unfolding of ubiquitinated proteins, and a core particle that contains the catalytic unit responsible for degrading the protein.
How does the proteasome recognize and degrade proteins?
-The proteasome recognizes polyubiquitinated proteins, unfolds them using the 19S regulatory particle, and then degrades them into small peptide fragments in the catalytic core.
What are the clinical implications of the ubiquitin proteasome pathway?
-Dysregulation of the ubiquitin proteasome pathway is associated with diseases such as cancer, neurodegenerative diseases like Alzheimer's and Parkinson's, and infectious diseases where pathogens may inhibit the pathway to evade degradation.
Outlines
🛡️ Ubiquitin Proteasome Pathway: Cellular Quality Control
This paragraph introduces the ubiquitin proteasome pathway, a critical cellular system for protein degradation. It underscores the pathway's role in maintaining cellular homeostasis by degrading misfolded, damaged, and non-functional proteins. The paragraph likens ubiquitin to a 'degradation tag' and the proteasome to a 'shredding machine'. It explains the pathway's mechanism involving E1, E2, and E3 enzymes that coordinate to mark proteins for degradation. The video uses a sniper analogy to illustrate how the proteasome selectively degrades proteins marked by ubiquitin, highlighting the importance of polyubiquitination as the key mark for degradation.
🔬 Detailed Mechanism of the Ubiquitin Proteasome Pathway
The second paragraph delves into the step-by-step process of the ubiquitin proteasome pathway. It describes the activation of ubiquitin by E1 enzyme, the transfer of ubiquitin to target proteins by E2 and E3 enzymes, and the recognition of polyubiquitinated proteins by the proteasome. The paragraph further explains the proteasome's structure, including the 19S regulatory particle and the catalytic core, which unfolds and degrades the protein. The video provides a visual analogy of the proteasome's operation, comparing it to a shredding machine that processes proteins. It also touches on the clinical relevance of the pathway, mentioning its association with diseases such as cancer and neurodegenerative disorders like Alzheimer's and Parkinson's.
Mindmap
Keywords
💡Ubiquitin
💡Proteasome
💡Protein Degradation
💡Cellular Homeostasis
💡Polyubiquitination
💡E1 Enzyme
💡E2 Enzyme
💡E3 Enzyme
💡Lysine
💡19S Regulatory Particle
💡Unfoldase Ring
Highlights
The ubiquitin proteasome pathway is critical for cellular protein degradation.
This pathway maintains cellular homeostasis by degrading misfolded, damaged, and non-functional proteins.
Ubiquitin is a small protein that tags proteins for degradation, acting as a 'degradation tag'.
The proteasome is a large complex that degrades ubiquitinated proteins, likened to a 'shredding machine'.
The pathway is compared to a sniper scenario, where ubiquitin tags help the proteasome identify target proteins for degradation.
Ubiquitin is activated by the E1 enzyme in an ATP-dependent manner.
The E2 enzyme, or ubiquitin conjugation enzyme, transfers ubiquitin to target proteins with the help of E3.
E3 enzymes coordinate with target proteins and facilitate the transfer of ubiquitin from E2, flagging them for destruction.
Polyubiquitination is the key mark for proteasome-mediated degradation.
Polyubiquitinated proteins are destined for degradation, unlike monoubiquitinated proteins which may not be degraded.
The proteasome consists of a 19S regulatory particle and a core particle, which contains the catalytic unit for protein degradation.
The proteasome recognizes polyubiquitinated proteins, unfolds them, and degrades them in an ATP-dependent process.
The clinical relevance of the ubiquitin proteasome pathway includes its association with cancer and neurodegenerative diseases.
Dysregulation of the UPS pathway is implicated in cancer development.
Neurodegenerative diseases like Alzheimer's and Parkinson's are linked to impairments in the ubiquitin proteasome machinery.
Pathogens can inhibit the proteasome pathway to evade immune system recognition.
The video provides educational content on the ubiquitin proteasome pathway with practical applications and clinical significance.
Transcripts
in this short video we'll talk about
ubiquitine proteasome protein
degradation pathway so ubiquitine
proteasome pathway is a system which is
very critical for the cell which
regulates protein
degradation question is what is the
utility of this pathway for a cell why
it is important for the cell because
this kind of pathway ensures that it
degrades misfolded damaged and basically
non-functional proteins to maintain
cellular homeostasis so one can imagine
this to be a quality control pathway as
well so there are two main components to
it one is ubiquitine which is a small
protein 76 amino acid long and that tags
the protein for degradation so it's kind
of like a degradation tag and then there
is a proteosome which is a large
proteolytic complex that degrades the
uated proteins which were previously
marked for degradation so it's kind of
like a shredding machine
now this kind of pathway is pretty
similar to this real life scenario
imagine this particular sniper has to
kill one particular uh person in a crowd
but how does the sniper recognize who is
the target person until and unless
somebody tags that person it's
impossible for the sniper to look at
that and here the person may be a spy
who pointed out this is the person to
kill and then the sniper can kill
similarly the proteosome is the sniper
proteosome doesn't know which particular
protein to degrade proteosome doesn't
know whether that protein is
nonfunctional aggregated or misfolded so
proteomes job is just like a sniper to
kill or to degrade and the main job is
done by the
polyubiquitinated tag which is provided
by these ubiquitin uh uh enzymes
basically there are E1 E2 and E3 enzymes
which in coordination flag the
particular protein with poly
ubiqutination Mark and that's the key
mark for degradation by
proteosome so let us talk about the
step-by-step process of ubiquitine
proteosome pathway so first of all the
E1 enzyme which is ubiquitine activating
enzyme activates the ubiquitine in an
ATP dependent manner then there is E2
protein which kind of is a conjugation
enzyme so it's known as ubiquitine
conjugation enzyme it transfers the
ubiquitine residues to a Target protein
and it does that with the help of e3 so
E3 kind of coordinates with the target
protein and E2 transfer the ubiquitine
protein into the target protein kind of
flagging them for Destruction so E3 is
the ubiqutin liase and it facilitates
the transfer of ubiqutin from the E2 to
the lysin residues of the target protein
always remember that lysin is the
residue that gets
ubiquitinated after poly ubiqutination
that means ubiqutination for several
times proteasome recognize this poly
ubiqutination tag and degrades the
protein just like a shredding machine so
in some word proteosome is kind of like
a molecular shredding
machine it's important to note that
polyubiquitinated proteins are destined
to be degraded so poly ubiqutination tag
is a tag that is interpreted for
degradation but mono ubiquit inated
proteins might not be degraded it's
basically a kind of like a protein
modification that can happen so it
doesn't require to be degraded but a
poly ubiquity ination tag would be now
let's talk about the proteosome a little
bit more so proteosome has different
component it has a 19s regulatory
particle which recognize ubiquitinated
protein unfolds them and eventually send
it to the core now the core which is
marked here in the red is the main
particle it has the catalytic unit which
literally uh degrades the protein and
chops off the protein like a shredding
machine so there are two things that are
happening one is recognition another is
destruction of the protein so here is a
kind of like cross-section view of the
proteosome where we can zoom and see the
head of the proteosome has the cap which
recognize the particular ubiquitylated
poly uated protein and channel those
proteins and unfold that protein through
sprad it through the catalytic core so
now we are going to look at that process
in detail so here is the cap here is the
unfold as ring so unfold as Ring's job
is to unfold the protein from its native
structure there is a central cylinder
which has the catalytic core shown in
yellow now here is a protein that gets
recognized by the cap using the
uated uh poly uated residue now notice
how the protein is threaded through the
unfold as ring to the catalytic core so
the unfold as ring literally rips off
the the protein into its primary
structure and pass it through this
narrow ring eventually what happens is
the catalytic core starts degrading the
protein and chops off into small peptide
fragments this is how proteosome works
so overall there are two things the
proteosome cap recognize the poly uated
protein and the translocation of the
protein happens to the catalytic core
which degrades the protein in an ATP
dependent manner so clinically utin
proteosome path is important for cancer
disregulation of UPS pathway or utin
proteosome pathway has been shown to uh
be associated with cancer it is
associated with uh neurod degeneration
for example Alzheimer's disease
Parkinson disease has impairment in
ubiqutin proteosome Machinery which pre
which leads to protein aggregation
because this is kind of like a quality
control
mechanism then there is in involvement
of these pathway in infectious disease
some of the pathogens literally inhibit
the proteosome pathway to prevent uh
things to be degraded so basically if
immunoproteasome doesn't degrade them
then it is never been recognized or
never be displayed on the class one MHC
molecule so that is why uh many
infectious pathogens suppress the
proteosome pathway so I hope this video
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