Molecular Structure of Proteasome

Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases.
Proteasomes are part of a major mechanism by which cells regulate the concentration of particular proteins and degrade misfolded proteins. Proteins are tagged for degradation with a small protein called ubiquitin. The tagging reaction is catalyzed by enzymes called ubiquitin ligases. Once a protein is tagged with a single ubiquitin molecule, this is a signal to other ligases to attach additional ubiquitin molecules. The result is a polyubiquitin chain that is bound by the proteasome, allowing it to degrade the tagged protein.[1] The degradation process yields peptides of about seven to eight amino acids long, which can then be further degraded into shorter amino acid sequences and used in synthesizing new proteins
The number and diversity of subunits contained in the 20S core particle depends on the organism; the number of distinct and specialized subunits is larger in multicellular than unicellular organisms and larger in eukaryotes than in prokaryotes. All 20S particles consist of four stacked heptameric ring structures that are themselves composed of two different types of subunits; α subunits are structural in nature, whereas β subunits are predominantly catalytic. The α subunits are pseudoenzymes homologous to β subunits. They are assembled with their N-termini adjacent to that of the β subunits.
The 19S particle in eukaryotes consists of 19 individual proteins and is divisible into two subassemblies, a 9-subunit base that binds directly to the α ring of the 20S core particle, and a 10-subunit lid. Six of the nine base proteins are ATPase subunits from the AAA Family, and an evolutionary homolog of these ATPases exists in archaea, called PAN (Proteasome-Activating Nucleotidase).[26] The association of the 19S and 20S particles requires the binding of ATP to the 19S ATPase subunits, and ATP hydrolysis is required for the assembled complex to degrade folded and ubiquitinated proteins. Note that only the step of substrate unfolding requires energy from ATP hydrolysis, while ATP-binding alone can support all the other steps required for protein degradation (e.g., complex assembly, gate opening, translocation, and proteolysis).[27][28] In fact, ATP binding to the ATPases by itself supports the rapid degradation of unfolded proteins. However, while ATP hydrolysis is required for unfolding only, it is not yet clear whether this energy may be used in the coupling of some of these steps.
The assembly of the proteasome is a complex process due to the number of subunits that must associate to form an active complex. The β subunits are synthesized with N-terminal "propeptides" that are post-translationally modified during the assembly of the 20S particle to expose the proteolytic active site. The 20S particle is assembled from two half-proteasomes, each of which consists of a seven-membered pro-β ring attached to a seven-membered α ring. The association of the β rings of the two half-proteasomes triggers threonine-dependent autolysis of the propeptides to expose the active site. These β interactions are mediated mainly by salt bridges and hydrophobic interactions between conserved alpha helices whose disruption by mutation damages the proteasome's ability to assemble.[43] The assembly of the half-proteasomes, in turn, is initiated by the assembly of the α subunits into their heptameric ring, forming a template for the association of the corresponding pro-β ring. The assembly of α subunits has not been characterized.

[@sakhawatshah2046]

Very brilliant... can understand the hardwork behind the scene...

[@hussainbiology]

thanks buddy... Only few can understand the work behind making

[@bandayiqbal8097]

I can't even imagine how much knowledge and hardwork is needed to make such a animation.......7 days are just a number.....U R the best..... thank You sir.

[@hussainbiology]

thanks Iqbal bhai.. Glad u can see/imagine the work behind the camera.... Yeah it takes everything to make videos like this

[@michaeleisenberg7867]

Shabir, I did some more reading. It seems endless. The proteasomes fascinate me. Apparently they require chaperones to be put together (actually this is obvious and intuitive). It's an area of active research--not well worked out. I am under the impression that most enzymes contain only a few amino acids at their active sites. And those AA's might be separated by many nonactive AA's along their primary structure. Only when the protein folds correctly into its tertiary form do those few active AA's line up next to each other to form the working part of the protein. Sometimes Fe, Zn and Mg is sprinkled in to hold a substrate in place or grab a loose electron. That brings us back to the proteasome. This behemoth not only contains many subunits but you can only imagine how many chaperones are involved. And before that all the polymerases, ribosomes and DNA/RNA. Every one of those proteins had to fold just right to make a proteasome. This verbose post brings me to my conclusion. What happened 4 billion years ago? For evolution to get it right it had to have working DNA which then lined up hundreds of AA's in just the right order so they would fold correctly and become an active enzyme. The proteasome is massive and its back story is an enigma. I think a lot of students marvel at the origin, construction and function the electron transport chain (especially ATP synthase with its spinning wheel and stator protein) . But I'll put up the proteasome as equally impressive. A lot had to go right 4 billion years ago for it to work and for us to be here today!!! Hallelujah!

[@michaeleisenberg7867]

Hello 👋 Shabir, I hope you are well.
Another very well organized and very well-thought-out video 📹. 👏👏👏💖💝💟
The colored 🎨 subunit animations are great!
I'd hate to get stuck inside a proteasome 😘.
I don't understand how the researchers 🔬 can take these things apart 🔧🔩 and figure out the form & function of each subunit. They do it without breaking 🔨 it! It's almost as impressive as how the whole thing evolved 🔮 in the first place?

[@hussainbiology]

Hello Dr. Mike.... first of all thanks for your kind words.... and yeah it is amazing how researchers are putting forward these mechanisms ...✌️

[@bandayiqbal8097]

The research is done by many researchers..... but it is really difficult to assemble all the data of each subunit...

[@michaeleisenberg7867]

@@bandayiqbal8097 That is a very interesting point that I never thought of. Thank you. If several labs across the world are working on different pieces of the proteasome, who compiles all the info into a cohesive chapter in a textbook 📚.

[@hussainbiology]

@@bandayiqbal8097 Thanks Iqbal.. Appreciate it

[@user-sl6fr9uh3t]

Dear sir .Who selects the un or miss folded protein to be degraded and how ubiquitin ligase selects the target protein, and how rpn 10 n rpn 13 captures target protein ,im thinking by ubiquitins . ur videos always full fill my day ❤huge respects to ur work sir

[@suzanneelsasser5521]

Engaging video! Technical point: in addition to Rpn10 and Rpn13, Rpn1 also captures ubiquitinated proteins. Also, Rpn10 doesn't dock onto Rpn1, though that would be very satisfying given that Rpn13 docks onto Rpn2.

[@ashirt2100]

Great Sir!!!! You are great!!!!God bless you

[@hussainbiology]

thanks for appreciation...God bless u too

[@shwethakrishna3716]

Thanks sir

[@hussainbiology]

My pleasure.
✌️

[@oliverkippes6043]

Great video, the planar structure helps a lot to undestand the organisation of the subunits.
I have a question about the catalytic subunits, as far as I know the mechanism inside the proteasome is started with a nucleophile attack from the N-terminal threonine residues and then a hydrolysation of the Intermediate. What causes then the different functions of the Subunits?

[@hussainbiology]

i have not touched the N Terminal degradation mechanism.

[@michaeleisenberg7867]

Shabir, I was reading in Wiki about the catalytic triads inside proteasomes. Absolutely amazing. The 3 active amino acids (the nucleophile, the base, and the acid) are widely separated along the primary structure of the enzyme but when it folds into its tertiary structure they are juxtaposed to form the functioning catalytic triad. Even more amazing is convergent evolution in which multiple different enzymes have evolved with similar catalytic triads. This is what I call more god particles. How did it happen? This stuff is mind boggling. en.wikipedia.org/wiki/Catalytic_triad

[@hussainbiology]

Thanks Dr Mike.. I have gone through the article and is really info packed.... Thanks for appreciation 😊😊

[@michaeleisenberg7867]

@@hussainbiology Shabir, I am glad you enjoyed the link. All your videos send me to the web for more info. Very inspiring!!! I am so amazed with how and what the scientists have discovered and figured out. All our little molecular machines busy at work...

[@hussainbiology]

@@michaeleisenberg7867 the Creator is Almighty...

[@michaeleisenberg7867]

@@hussainbiology For sure!

[@biologystudent1790]

Hello sir, I want to make educational videos in animated form like you so pls guide me ....

[@hussainbiology]

mail me at [e-mail]✌️

[@prathikkyasarapu1266]

Dear hussain sir , would you make a video on types of Rna splicing sir please...thank you so much sir , i learned many concepts from your channel ... i am grateful sir.. thank you so much..:)

[@hussainbiology]

Surely Prathik, bhai.... Will consider making video on that

[@prathikkyasarapu1266]

@@hussainbiology Thank you sir

[@syed-wd8ib]

beta 5 shows chymotrypsin like activity but you said it cleaves after hydrophobic a.a but chymotrypsin cuts after aromatic aa

[@hussainbiology]

aromatic amino acids do have hydrophobic pockets

[@hussainbiology]

Phenylalanine , tryptophan and tyrosine... all 3 are hydrophobic as well as aromatic

[@shaguftayaseen8574]

❤

[@hussainbiology]

✌️