Ubiquitination of Proteins and Protein Degradation
Summary
TLDRThis video explains the process of ubiquitination, where a ubiquitin protein is covalently linked to a lysine residue of target proteins. The purpose of ubiquitination is to tag proteins for degradation, especially misfolded or unnecessary proteins, by marking them for destruction by proteasomes. The video describes the role of enzymes E1, E2, and E3 in the ubiquitination process, and explains how the tagged proteins are degraded by proteasomes into peptides. Additionally, it mentions prions, which resist degradation by proteasomes. Viewers are encouraged to like and subscribe for more content.
Takeaways
- 🔗 Ubiquitination is the process where ubiquitin proteins are covalently linked to lysine residues of target proteins.
- 🔬 Ubiquitination marks proteins for destruction or degradation, particularly misfolded, toxic, or unnecessary proteins.
- ⚙️ Ubiquitination is also involved in some signaling pathways, helping switch them on or off by degrading proteins.
- ⚡ The ubiquitination process is initiated by three types of enzymes: E1 (activating enzyme), E2 (conjugating enzyme), and E3 (ligase enzyme).
- 💡 E1 enzyme activates ubiquitin by forming a thioester bond between ubiquitin and itself, in an ATP-dependent process.
- 🔄 E2 enzyme transfers the activated ubiquitin from the E1 enzyme to its own cysteine residue.
- 🎯 E3 enzyme facilitates the transfer of ubiquitin from E2 to the lysine residue of the target protein, forming an isopeptide bond.
- 📏 Proteins can be mono-, multi-, or poly-ubiquitinated depending on the number of ubiquitin molecules attached.
- 🏭 The degradation of ubiquitinated proteins is carried out by proteasomes, particularly the 26S proteasome, which consists of 20S proteasome and 19S caps.
- 🧩 Proteasomes break down the tagged proteins into short peptides, recycling ubiquitin in the process.
Q & A
What is ubiquitination?
-Ubiquitination is a biochemical process in which a ubiquitin protein is covalently linked to the lysine residue of target proteins. This process often tags proteins for degradation.
What type of bond is formed between ubiquitin and the lysine residue of the target protein?
-An isopeptide bond is formed between the lysine residue of the target protein and ubiquitin.
What is the purpose of ubiquitination?
-The purpose of ubiquitination is to tag proteins for destruction or degradation, particularly proteins that are misfolded, toxic, or no longer needed by the cell. It can also play a role in regulating signaling pathways by degrading specific proteins.
What enzymes are involved in the ubiquitination process?
-The enzymes involved in ubiquitination include ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligase enzymes (E3).
What role does the E1 enzyme play in ubiquitination?
-The E1 enzyme, also known as ubiquitin-activating enzyme, links itself with the carboxyl end of ubiquitin through a thioester bond. This step is energy-dependent and requires ATP.
How does the E2 enzyme contribute to ubiquitination?
-The E2 enzyme, or ubiquitin-conjugating enzyme, transfers the activated ubiquitin from the E1 enzyme to its cysteine residue, preparing it for the next step in the process.
What is the function of the E3 enzyme in ubiquitination?
-The E3 enzyme, or ubiquitin ligase, facilitates the transfer of ubiquitin from the E2 enzyme to the lysine residue of the target protein, forming an isopeptide bond between them.
What are the different types of ubiquitination?
-Proteins can undergo mono-ubiquitination (single ubiquitin attachment), multi-ubiquitination (multiple ubiquitin molecules attached at different sites), or poly-ubiquitination (a chain of ubiquitins attached to a single lysine residue).
What is the structure of the proteasome, and how does it function in protein degradation?
-The proteasome consists of two alpha rings and two beta rings, forming the 20S core particle. This core particle is capped by a 19S regulatory particle, forming the 26S proteasome. The proteasome recognizes ubiquitinated proteins, degrades them into peptides, and recycles the ubiquitin molecules.
What happens to prions during the degradation process?
-Prions, which are misfolded proteins, are resistant to degradation by proteasomes. This makes them difficult to degrade, leading to the persistence of prion-related diseases.
Outlines
👋 Introduction to Ubiquitination
The video begins with an introduction to the concept of ubiquitination, explaining that it is a biochemical process where ubiquitin proteins are covalently linked to lysine residues of target proteins. This process, driven by enzymes, tags proteins for degradation. Ubiquitination mainly occurs in proteins that are misfolded, toxic, or no longer useful to the cell. Additionally, it plays a role in regulating signaling pathways by marking proteins for destruction. The video briefly touches on how this tagging leads to protein degradation through the action of proteasomes, a topic that will be discussed further.
🔧 Enzymes Driving Ubiquitination
The discussion then shifts to the enzymes involved in ubiquitination. There are three key enzymes: E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin ligase). The E1 enzyme binds to the ubiquitin protein through a thioester bond, a process requiring ATP. The activated ubiquitin is then transferred to the cysteine residue of E2. Finally, E3 transfers the ubiquitin from E2 to the target protein, marking it for degradation. This section explains the step-by-step role of these enzymes in facilitating the ubiquitination process.
🔄 Detailed Mechanism of Ubiquitination
A more detailed explanation of the ubiquitination mechanism is provided in this section. Ubiquitin, activated by the E1 enzyme, is transferred to E2 and ultimately conjugated to the target protein by E3 ligase. The bond formed between the lysine residue of the target protein and the ubiquitin is an isopeptide bond. The target protein can be tagged with one or multiple ubiquitins (mono- or poly-ubiquitination). The ubiquitinated protein is now ready for degradation by proteasomes.
🧬 Structure and Function of Proteasomes
The proteasome is described in detail, showing its structure with two alpha and two beta rings that form a core, referred to as the 20S proteasome. The 19S cap is attached to either one or both alpha rings, creating the fully functional 26S proteasome. The role of the 19S cap in recognizing ubiquitin-tagged proteins is highlighted. Once recognized, the protein is pulled into the proteasome and broken down into peptides, while the ubiquitin is recycled for future use.
🧩 Final Steps of Protein Degradation
This section wraps up the explanation of protein degradation by discussing how the proteasome breaks down ubiquitinated proteins into short peptides. It also mentions prions, which are misfolded proteins resistant to degradation by proteasomes. This resistance can lead to certain diseases. The video concludes with a brief recap of how ubiquitination tags proteins for degradation and how proteasomes carry out this degradation process.
👍 Conclusion and Call to Action
In the final part, the video wraps up by summarizing the key points discussed, focusing on the ubiquitination process and its role in protein degradation. The presenter encourages viewers to give a thumbs up if they enjoyed the video and to subscribe to the channel for more content.
Mindmap
Keywords
💡Ubiquitination
💡Proteins
💡Lysine Residue
💡Isopeptide Bond
💡E1 Enzyme (Ubiquitin-activating enzyme)
💡E2 Enzyme (Ubiquitin-conjugating enzyme)
💡E3 Ligase (Ubiquitin ligase)
💡Proteasome
💡Prions
💡ATP
Highlights
Ubiquitination is a biochemical process where ubiquitin protein is covalently linked to the lysine residue of target proteins.
The bond formed between ubiquitin and the lysine residue of the target protein is an iso-peptide bond.
Ubiquitination marks or tags proteins for destruction or degradation, particularly misfolded, toxic, or unnecessary proteins in the cell.
Ubiquitination also plays a role in regulating signaling pathways by marking proteins for destruction, enabling the activation or deactivation of pathways.
Three main enzymes drive the ubiquitination process: E1 (activating enzyme), E2 (conjugating enzyme), and E3 (ligase enzyme).
E1 enzyme links with the carboxyl end of ubiquitin protein through a thioester bond in an ATP-dependent manner.
E2 enzyme transfers activated ubiquitin from the E1 enzyme to the cysteine residue of the E2 enzyme.
E3 ligase transfers ubiquitin from the E2 enzyme to the lysine residue of the target protein, forming an iso-peptide bond.
Proteins can undergo mono-ubiquitination, multi-ubiquitination, or poly-ubiquitination.
The degradation of ubiquitinated proteins occurs in the proteasome, a multi-subunit complex responsible for breaking down proteins into peptides.
The proteasome structure consists of two alpha rings and two beta rings sandwiched between the alpha rings, forming the 20S proteasome.
The fully functional 26S proteasome includes a 19S cap attached to either one or both alpha subunit rings of the 20S proteasome.
The 19S cap recognizes the ubiquitin chain on the tagged protein and guides it into the proteasome for degradation.
The ubiquitin proteins are recycled after degradation, and the target protein is broken down into short peptides.
Some misfolded proteins, like prions, resist degradation by proteasomes due to their structural properties.
Transcripts
oh hello friends in this video we'll be
discussing about ubiquitination of
proteins and also we'll be discussing
about protein degradation first of all
let's see what ubiquitination is it is
the biochemical process while ubiquitin
protein is covalently linked it to
lysine residue off target proteins if we
see it diagrammatically we see we have a
target protein like this as shown in the
figure and on the Left we have a
ubiquitin protein shown as a blue dot
and in this process of linking ubiquitin
with protein which is initiated by
enzymes and we get the ubiquitin
attached to it in this manner and it
must be noted here the bond between
lysine residue and the ubiquitin is the
iso peptide bond
so in nutshell we can say proteins are
getting tagged by you acute in protein
on their lysine residue but what's the
purpose of this ubiquitination the
purpose of ubiquitination is to mark or
tag the proteins for destruction or
degradation the ubiquitination
occurs on those proteins which are Mis
folded or toxic proteins or on those
proteins which are of no use in the cell
ubiquitination also happens to be part
of some signaling pathways in order to
switch on and switch off the pathways by
the destruction of proteins so we say
ubiquitination tags the proteins for
degradation and the rest of the work is
done by proteomes which we will see
later on in this video now let's jump
towards the enzymes first that drive the
ubiquitination process first of all we
have you acute in activating enzymes in
short we say it's even enzyme this even
enzyme links itself with the carboxyl
end of cuba cute in enzyme through
thirst or bond and this step is energy
dependent so it needs ATP's then we have
ubiquitin conjugating enzyme e 2 which
transfers the activated u Akutan from
even towards the cysteine residue of e 2
enzyme and finally we are you acute in
ligase enzyme called III enzyme whose
function is transfer the Ubiquiti into
that target protein
now let's see the mechanism of your
coordination process in detail the
structure of ubiquitin protein is shown
in the diagram
while we see you bruiting attach it to a
carboxyl and then to this the even
enzyme acts on it in presence of ATP and
in this relation the ubiquitin is linked
to the even enzyme as shown in the
structure by Pauling thioester bond with
even enzyme then e2 enzyme comes in and
transpose the activated u Akutan from
even towards the cysteine residue of e
to enzyme now the ubiquitin is
conjugated to the e2 enzyme and we have
a target protein which needs to be
tagged it with this ubiquitin protein so
finally the last enzyme that's III known
as ubiquitin ligase comes in and
transpose the ubiquitin from e2 towards
the lysine residue of target protein by
forming the ISO peptide bond between
lysine and Ubiquiti and also keep this
thing in mind the proteins can be mono
ubiquitinated Multi ubiquitinated or
even poly ubiquitinated so now we have
ubiquitinated protein ready to be
decorated and for this degradation
process we need protostomes if we see
the structure of proteasome we have two
alpha rings and also two bitter rings
which are sandwiched between alpha rings
as shown in the diagram this makes us
the 20s proteasome and to this 20s
proteasome the 19's cap is attached to
either one or both alpha subunit rings
and this completes the structure thus
forming as the 26s proteasome which is
fully functional to decorate the
proteins into peptides then the next
step of protein degradation will be
recognition and the Tiger protein is
recognized by 19's cap when it binds to
the ubiquitin chain and pushes the rest
of the protein into the proteasome
thus recycling back the ubiquitin
proteins and we get the target protein
converted into short peptides by the
action of proteome and also remember
that there are some proteins miss folded
proteins which are called prions which
need to be degraded but are not degraded
due to the
stens of prions for proteolysis by
protozoans
so this is all about ubiquitination of
proteins how ubiquitination of proteins
is done and how then proteins are
subjected to that degradation by
protostomes so this is all about it I
hope you liked the video if you liked it
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