The Proteasome (2024) by Etsuko Uno wehi.tv
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- เผยแพร่เมื่อ 22 พ.ค. 2024
- This Proteasome is a large enzyme complex that breaks down old or damaged proteins into smaller pieces for cellular maintenance and recycling.
Created with structural data from X-ray crystallography and cryo-electron microscopy, this animation provides a detailed visualization of the proteasome's molecular machinery. Presented here are critical steps of protein degredation including ubiquitin tagging, unfolding by the regulatory particle, and proteolytic degradation within the core particle.
Featured structures include 6MSB, 6MSD, 6MSE, 6MSG, 6MSH, 6MSJ, 6MSK, 5LE5, 2KDE, 2KR0, 6FVW, 5L4K, 6U19. All can be found at RSCB Protein Data Bank (www.rcsb.org/). - วิทยาศาสตร์และเทคโนโลยี
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WONDERFUL WORK. We are privileged to live in this era. Thanks.
Well done! I really like the chemical reality of constant motion, and bits bouncing all over the place.
We are far away from processing molecular structures individually, yet it is happening inside of us billions of times a day, for hundreds of millions of years.
Crazy stuff
It's estimated to be around 30 to 40 trillion times per SECOND in all our cells working in concert to give us this thing we call life.
I find it so wonderful how all of this came about from random chaos, i find that the idea that there is some greater will or being some how brought about complexity to be rather boring, it really undermines the sheer scale of it all, with such few rules to follow, infinite possibilities come forth, complexity from the mundane, i find it all beautiful.
@@themushroominside6540 We all came from a billions of years old microscopic 3D Tetris game, I enjoy describing it like that because it's not entirely correct nor is it entirely incorrect
I don't know what you mean by that, we can process individual molecules, just not with the same speed and efficiency.
life is a very complex engine, aiding the universe by accelerating the transition from low entropy to high entropy
I have always been driven to understand how life processes work. Seeing your work here, for me is like going to the movies. Thank you.
This animation is mind-blowing ! Thank you
Beautiful molecular machines. I've learned so much from Drew's team.
Wow, just wow so much... a thousand times WOW! To see all of this so clearly, what a miracle. The three chambers of the core? I had no idea that's how this worked. Thank you so much!!!!!
I'm actually in awe watching this, most importantly that our bodies can do that, but also that we've got to a point where we can communicate and explain it ❤️
those are amazing animations. Quite different to reading about this in a book. This must be very helpful for students and professionals trying to learn and understand the subject better.
the heavy use of granular synthesis and foley really bring home the micro mechanics - great stuff!
Incredible animation. Thanks for sharing the knowledge.
Props to the artist, The visuals is just.. I just love it XD
This is fantastic, such a good way to show what is happening on a molecular level.
Subscribed because I can't get enough of these molecular animations. Amazing!
Very interesting video. It's unbelievable how perfectly these little machines work and how they are optimally co-ordinated throughout the entire organism.
It's actually completely believable... Which is what makes it so spectacular!
It might seem like it's perfect, but it's far from perfect. There are many errors, but what saves the situation is the sheer amount of these particles and repairing mechanisms. This is all thermal movement and we only see perfect cases modelled.
Thank you for your contribution. Of course, nothing in the universe is perfect. But the apparent pursuit of perfection in micro- and molecular biology and the incredible adaptability are nevertheless breathtaking. Kind regards.
This is animated and educational; of course it looks "co-ordinated" or perfect.
Can't believe that there are actually people that denies the existence of these beautiful molecular bio-machines
Fear of the unknown does certainly hold much of humanity back. We're like goldfish being afraid of a Lego cause it looks weird.
Calling them "people" is a massive stretch. They are morlocks at most.
As always, the sound design is top notch!
Babe! Wake up! WEHI just uploaded another banger short film!
This would have made learning biochemistry so much easier back when I took it 30 years ago.
amazing, thanks a lot WEHImovies team! we love you.
Poder escuchar el video en español es un trabajo que nadie quiere hacer, pero se hace. Gracias por los videos!!
Just when you thought you had seen it all, another fascinating machine you took for granted, who would have thought, specialized garbage collection and recycling of reusable parts. I thought stuff just dissolved or something, more like inorganic chemistry, but it’s all very specific machinery, built atom by atom.
Learned something. Makes my day.
These little molecular machines are remarkable.😊
I love it! This is so beautiful and creative. I do 3D animations and so I am doubly appreciative of your creativity.
Congratulations! Such a wonderful narration and animation!! 😍✨✨
Wow awesome
Wow, many thanks
This is the craziest thing I watch today.
I am most curious, is the video an animation or a simulation?
In any case, it is incredible to be able to have insight into this machinery of life.
Animation created with structural data from X-ray crystallography and cryo-electron microscopy. You can learn more about our pipeline in this tech talk:
th-cam.com/video/qbyzEiBvbXw/w-d-xo.htmlsi=klhfph5aOgX3fFjs
すばらしい視覚化技術
How could anyone watch this and not click Like?
There are probably only two things left that still put me in a state of child-like state of awe. One is that even if our universe would be the only one in existence "right now" (which I don't think so), there was quite definitely some universe before our big bang because our big bang must have been caused by some underlying situation and that goes back till forever. This "something" instead of "nothing" situation has to go back to eternity which makes my brain glitch thinking about that. The other thing that does that for me are these beautiful molecular machines capable in some cases of handling even individual electrons. I am absolutely certain that it is possible to make any creature biologically immortal (dictators will be an issue heh) once you can fully (or sufficiently for that purpose) understand and control these biological processes, because albeit extremely complex, we are clearly "just" a mind boggling chunk of molecular machinery and if you can keep the components in a specific state without degradation as it happens naturally through DNA getting damaged, proteins then being produced with defects, one could live for 1000 years if he can keep himself occupied and entertained. Or we could regrow missing limbs, eyes and so on. The possibilities are thrilling (with some ethical questions to be solved for sure).
I have no words to express how interesting this is! Wow. How do you even get to know it?
From the combined work of thousands of researchers over the last 50 to 100 years.
Look up Bio-Chemistry educational materials.
We have multiple methods to acquire the 3D structures (atom by atom) of molecules, X-ray Diffraction/Crystalography is used most of the time. From there, we either: 1. Run a simulation using the gathered 3D structure data, or 2. Continue taking snapshots of the same protein in its different states to get a sort of animatic of its function/behavior.
This is called Structural Biology.
Explanation of molecular animation production by wehi.tv
th-cam.com/video/qbyzEiBvbXw/w-d-xo.htmlsi=Rd7SUlklMvl_e4hF
How does it know what to do? It's amazing 🤯
Proteins and enzymes get their function from their shape and distributions of electrical charges. It’s very complicated but basically all of cellular biology is based on how much free energy (obtained from ATP breakdown into ADP) is in a system, which causes changes in protein shape, which moves charges around in the structure.
Very good question. It doesn’t “know” really. A protein is a large molecular puzzle, made from thousand of atoms. Every atom may possess a positive or negative charge (or neutral if no net charge). So, you have a 3D puzzle with different magnetic properties in different parts of the puzzle. You throw 2 proteins together and the magnetic interactions will be really interesting. Evolution, after millions of years, selects those structures that yield advantages for survival. We live in a wonderful universe. Greetings.
@@maxwellsimon4538 Not every protein requires ATP to function. Sometimes, the ambient energy (heat) of the cytoplasm is enough for the protein to function as a catalyst for a chemical reaction; other times, it uses other molecules as its source of energy such as NADH, sometimes it's the substrate itself.
@@Gelatinocyte2 that's true too
@@javiermachin1 Electrical, not magnetic.
This is so cool. Remind me of the day studying cell cycle and cellular biology.
Can you make a video about chaperone and protein folding?
So, has anyone yet thought about using or modifying these guys to fight Prions?
Prions are not just misfolded, they are misfolded and stable... Cannot think of a way to detect such a thing.
Dang new ones dropped and i did not know.
Amazing!
While I'm fully behind the theory of evolution, I can't imagine how something like this would evolve... it blows my mind! Great video!
What helped me is to realize that most proteins are just repurposed, slightly modified copies of other proteins. You can find the same motive from the beta subunit of the proteasome core in thousands of different serine-threonine proteases all over our genome and genomes of other organisms. It only really needs a small number of new inventions to get things moving, after that, it's just endless copying and reiteration.
Might be a stupid question, but if the proteins are cut randomly, shouldnt, eventually, this machine create tiny harmful peptides? Like, these peptides could interact with other things in unwanted ways and cause damage. Is this possible? If no, why not? If yes, then how the does the body manage these harmful peptides?
That's a good question, I'm not sure, I was curious about the same thing, this stuff is wild.
@@davidsiriani9586 Each enzyme "cuts" only in particular places.
Proteases usually only recognize/interact with certain pairs or triads of amino acids. So perhaps there was at one point some time ago where the random segments were harmful to the cell, but it probably isn't nowadays due to Natural Selection.
The cut peptides are quite inert and being short peptide chains that are floating around the cytosol, they would be further cut by proteases floating around the cytosol as well into single amino acids and repurposed by ribosomes either cytoplasmic or ribosomal to make new proteins. I think you are correct that maybe if these peptides accumulated and could maneuver freely around the body they might make protein aggregates or cause other damages to cells (like several disease states with protein clusters), but given the cellular proteases that can snip these peptides to bits rather quickly and then rapidly re-use them for protein synthesis, I don't think you run into this issue with normal physiology. (there are definitely disease states were excess breakdown of proteins or other biological molecules results in accumulation of harmful byproducts)
@@nathanlau8073 That's a great answer! Thank you!
If you don't mind I have another one about this stuff:
if the proteases in the proteasome can cut proteins and are themselves proteins that means they get made by ribosomes which are made up of proteins... so how do the ribosomes make the proteases without being cut by them?
Wow. By far one of the best molecular animations I've ever seen!!!
I think you've really captured the frenetic grace of the processes in an aesthetically pleasant way, great job everybody.🌞💚🐾🐾🐾
I feel like a big squishy robot now..:::🛸🧬🌌🙉
woooooo it was awesome!
babe! wake up! new wehi video!!
Great👀
Magique!
fascinating
What program was used to create this animation
wehi.tv animation pipeline
th-cam.com/video/qbyzEiBvbXw/w-d-xo.htmlsi=Xrr303O5T7OxrcRm
I have a couple questions if anyone is up for them:
• How efficient is the recycling system? Particularly, what percentage of damaged proteins fail to get recycled?
• Are the number of Proteasomes in a cell comparable to the number of Ribosomes?
• How accurate are the systems which attach the ubiquitin to proteins?
• Do Proteasomes operate both inside and outside the nucleus?
I have some answers for you!
a) The system is very efficient - all of those peptides will go on to be used within the cell. The raw matter is not lost, the only inefficiency is an energy one, I believe ATP is used to run the unfolding machinery of the proteasome, and more ATP will be needed to put new proteins back together,
b) Yes, there are many ribosomes, and many proteasomes - although the exact numbers are not important, what is is that the proteasome is only one mechanism of many recycling mechanisms your cells have for facilitate resource turnover within your cell. Thus the ratio of proteasomes to ribosomes is not really important as your question presumes. Google Autophagy as that is the true cellular recycling boss, proteasomes are more "precision" recycling machines.
c) They can be extremely perfectly accurate (dictated by the exact jigsaw fingerprint of ubiquitin binding of the target protein, and a facilitator signaling protein) but sometimes they are more relaxed, for example you may release a protein temporarily to attach ubiquitin to a lot of stuff as a stress response, and itll last a while then degrade after a time.
d) Yes.
Hope that helps, have a good day =)
When your proteasome goes:
*nom-nom-nom-nom-nom-nom*
*poop-poop-poop-poop-poop-poop*
I felt that, literally.
Loved the animation! Other sources, however, indicate a seven-fold symmetry, not 6. This may be significant as both inflammasomes and apoptosomes have a 7-fold symmetry. Many complex proteins have subunits in multiples of 2, 3, or 5. Seven is the largest prime number of multiple subunits in any protein, and (significantly?) these proteins all have roles in defense. As far as I know, nothing has subunits in multiples of 11.
I think there are *some* species whose proteasomes have 7-fold symmetry.
Not every protein or complex is the same in every cells. Even within the human body, there are proteins that are different between organs (e.g. hexokinase in brain cells is different from other cells).
@@Gelatinocyte2 As far as I know, 7-fold is the largest prime describing symmetry in proteins. Every protein I've run into with such a symmetry is involved in some form of defense (inflammasome, apoptosome). Sure, there are some proteins that vary, even in the same organism, such as M class antibodies with 6 (not 5) subunits. I just haven't found anything with a 7-fold symmetry that didn't have some role in defense, but I'd love it if someone could either find one, or come up with a rationale of why they don't exist.
Omg this video is so good
Amazing! I have 2 questions:
1 is this a simulation of the process or a 'representative' hand-made/procedural animation?
2 where does the proteasome get the energy for this process?
Thought of 2 more questions:
3 what's the time slow-down factor for what we're seeing as compared to the real process?
4 how many of these proteasomes are active simultaneously in the typical human cell?
This excellent talk on how the animations were produced answered two of my questions:
m.th-cam.com/video/qbyzEiBvbXw/w-d-xo.html
Time is slowed down by a factor of about a billion, and is derived from actual molecular simulations, however the animation is hand-tuned a fair bit to make it read more clearly for the viewer (reality would be way too messy to understand!)
Where does the motor take energy for its work?
Does untangling protein take energy or release energy?
Cutting stage looks like being powered by chaotic movement. Is it the same with motor: it works like a diod allowing chaotic movement down the pipe, but blocking reverse movement? (I think that explanation would delete the need in source of energy).
I think it uses ATP, it's just not shown in the video for clarity sake.
We are ALIVE! 😮
Re-uploaded, why?
Fixed typo in credits.
@@WEHImovies
Oh, thanks for replying.
What say you about the Association Induction Hypothesis?
A real challenge for those who create molecules, in turn creating the pair that recycles it.
cool
Nice movie
How are these damaged proteins identified?
Just like a molecular scale office paper shredder...
Imagine this but the proteins 100 × more jiggley and fluid
that is how a plumbus is made
Looks like a woman in a green dress with a yellow flower in her pink hair
it releases peptides, ribosome needs tRNA+aminoacid. how peptide (2-25 length) becomes an aminoacide is quite unclear.
There are smaller proteases which digests these peptide chains further. The main purpose of the proteasome is to unfold proteins, and break them down into manageable chunks that proteases can process.
I love this level of verisimilitude!
But could someone with expertise please explain just how close to reality these videos come? The colors are artifice, of course, but how about the rest?
30 min presentation on wehi.tv animation, what is real science and what is art
th-cam.com/video/qbyzEiBvbXw/w-d-xo.htmlsi=itxbkKV5ELY2ua4j
Luckily, all those noises our proteasomes make are fake. Otherwise we couldn’t sleep at night ;-)
Medical/cellular terminology is crazy to me. Proteins are broken down to amino acids, which are then cut down to peptides. Just name it like Pokémon where the biggest is called the Proteinizoid and the smallest is called Prota.
Wrong way around; it's "broken down into peptides, which are then cut down to amino acids". Remember: "peptides" are chains of amino acids, and is just a fancy word for "unfolded proteins"; proteins are just structured chains of amino acids.
TH-cam compression algorithm hates this video
Looks a bit like a mermaid
If everything is made of proteins, how does the proteasome not recycle itself?
she is smart
It does. By that I mean another proteasome breaks down the decommissioned one.
I know it's a very human question but WHY?
How the f CK is this even possible
Evolution created this?
It’s beautiful either way.
@@waluigihentailover6926 Beautiful? Like a fish processing boat.
yep, it's pretty neat isn't it?
Yes, of course. Why do you deny the fundamental principle of Biology?
@@weltschmerzistofthaufig2440 How? How would it happen?
Biology is too complicated for me
The idea of a "Creator" is such a silly superstitious idea with exactly zero evidence.