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<StructureSection load='' size='350' side='right' scene='41/417543/Cv/1' caption='Yeast proteasome 20S core complex with salinosporamide derivative, [[3gpt]]'>
<StructureSection load='' size='350' side='right' scene='41/417543/Cv/1' caption='Yeast proteasome 20S core complex with salinosporamide derivative, [[3gpt]]'>
== Function ==
== Function ==
[[Proteasome]] (PRTS) are large protein complexes which degrade unneeded proteins into small polypeptides<ref>PMID:22350895</ref>.  The '''26S PRTS''' is composed of a central '''20S core particle''' which contains 4 stacked rings each with several members and two 19S caps.  The 19S cap is composed of a base with 10 proteins six of which are ATPases and a lid which contains 9 proteins which bind polyubiquitin. <br />
[[Proteasome]] (PRTS) are large protein complexes which degrade unneeded proteins into small polypeptides<ref>PMID:22350895</ref>.  The '''26S PRTS''' is composed of a central '''20S core particle''' which contains 4 stacked rings each with several members and two 19S caps.  The 19S cap is composed of a base with 10 proteins six of which are ATPases and a lid which contains 9 proteins which bind polyubiquitin. <br />
*'''13S PRTS''' is a PRTS core intermediate containing α ring, partial β ring and 3 chaperones<ref>PMID:33846632</ref>.
*'''15S PRTS''' is half of an 20S PRTS and upon dimerisation forms the mature 20S PRTS<ref>PMID:32442437</ref>.
For more details see [[3unb]].
For more details see [[3unb]].


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== 3D Structures of Proteasome ==
== 3D Structures of Proteasome ==
[[Proteasome 3D structures]]
[[Proteasome 3D structures]]
 
== See Also ==
[[PROTAC]] (Proteolysis-Targeting Chimera), an alternative to conventional enzyme inhibitors, by enabling proteasome induced degradation of the target protein.
</StructureSection>
</StructureSection>
== 3D Structures of Proteasome ==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|
* Proteasome 20S core
**[[4r3o]], [[5le5]], [[5lex]] – h20S core – human<br />
**[[1iru]] – 20S core - bovine<br />
**[[3une]] – m20S core – mouse<br />
**[[3unh]] – m20S core (immuno)<br />
**[[3gpt]], [[3gpw]], [[1g0u]], [[5cz4]] – y20S core - yeast<br />
**[[1ryp]], [[3wxr]], [[4qux]], [[4quy]], [[4qv0]], [[4qv1]], [[4qv3]], [[4qv4]], [[4qv5]], [[4qv6]], [[4qv7]], [[4qv8]], [[4qv9]], [[4y8r]], [[4y9y]], [[4ya1]], [[4ya4]], [[5bxl]], [[5cgf]], [[5cza]], [[5d0w]] - y20S core (mutant)<br />
**[[3c91]], [[3c92]], [[1pma]], [[3j9i]], [[5vy3]], [[6bdf]], [[5vy4]] – Ta20S core - ''Themoplasma acidophilum'' - Cryo EM<br />
**[[3h4p]] – 20S core – ''Methanocaldococcus janaschii''<br />
**[[2h6j]], [[1q5r]] – Re20S core (mutant) – ''Rhodococcus erythropolis''<br />
**[[1q5q]] - Re20S core<br />
**[[1j2q]] – Af20S core - ''Archaeoglobus fulgidus''<br />
**[[3mfe]], [[3mi0]], [[2fhg]] – Mt20S core – ''Mycobacterium tuberculosis''<br />
**[[3mka]], [[3hfa]] – Mt20S core (mutant)<br />
*Proteasome 20S+activator protein
**[[4v7o]], [[5nif]] – y20S core+ Blm10 <br />
**[[1z7q]], [[1fnt]] – y20S core+PA26<br />
**[[3ipm]], [[3jrm]], [[3jse]], [[3jtl]], [[1ya7]], [[1yar]], [[1yau]] - Taa-PRTS chains A-G+ Tab-PRTS chains H-N+PA26 chains O-U <br />
**[[5lzp]] - Mt20S subunits a+b + BPA - Cryo EM<br />
**[[6bgo]], [[6bgl]] – Mt20S + activator<br />
*Proteasome 20S+inhibitor
**[[4r67]] – h20S + cancer drug<br />
**[[5ley]], [[5lf0]], [[5lf1]], [[5lf3]], [[5lf4]], [[5lf7]], [[5lez]], [[5lf6]] - h20S + inhibitor<br />
**[[5a0q]] - h20S + substrate analog<br />
**[[6avo]]  – h20S core + inhibitor<br />
**[[3unb]], [[3unf]] – m20S + inhibitor<br />
**[[3hye]], [[3gpj]], [[3dy3]], [[3dy4]], [[3e47]], [[3d29]], [[3bdm]], [[2zcy]], [[2gpl]], [[2fak]], [[2f16]], [[1jd2]], [[1g65]], [[3mg0]], [[3mg4]], [[3mg6]], [[3mg7]], [[3mg8]], [[3oeu]], [[3oev]], [[3okj]], [[3shj]], [[3un4]], [[3un8]], [[3sdi]], [[3sdk]], [[4fzc]], [[4fzg]], [[4gk7]], [[4eu2]], [[4inr]], [[4int]], [[4inu]], [[4jsq]], [[4jsu]], [[4jt0]], [[4qwx]], [[4qzz]], [[4r17]], [[4r18]], [[4rur]], [[5ahj]], [[4y69]], [[4y6v]], [[4y6z]], [[4y70]], [[4y74]], [[4y75]], [[4y77]], [[4y78]], [[4y7w]], [[4y7x]], [[4y7y]], [[4y80]], [[4y81]], [[4y82]], [[4y8g]], [[4y8h]], [[4y8i]], [[4y8j]], [[4y8k]], [[4y8l]], [[4y8m]], [[5dki]], [[5dkj]], [[5l52]], [[5l54]], [[5l55]], [[4y6a]], [[4y84]], [[4y8n]], [[4y8o]], [[4y8p]], [[4y8q]], [[4y8s]], [[4y8t]], [[4y8u]], [[4y9z]], [[4ya0]], [[4ya2]], [[4ya3]], [[4ya5]], [[4ya7]], [[4ya9]],  [[5jhr]], [[5jhs]], [[5lai]], [[4r02]], [[2zcy]], [[5bou]], [[5laj]], [[6gop]] – y20S core+inhibitor<br />
**[[4qxj]], [[4qz0]], [[4qz1]], [[4qz2]], [[4qz3]], [[4qz4]], [[4qz5]], [[4qz6]], [[4qz7]], [[4qzw]], [[4qzx]], [[4r00]], [[4r02]], [[5cgg]], [[5cgh]], [[5cgi]], [[5d0t]], [[5fgh]] – y20S (mutant) + inhibitor<br />
**[[4hnp]], [[4hrc]], [[4hrd]], [[4lqi]], [[4ltc]], [[4q1s]] - y20S core + antibiotics<br />
**[[4nnn]], [[4nnw]], [[4no1]], [[4no6]], [[4no8]], [[4no9]], [[4qby]], [[4qlq]], [[4qls]], [[4qlt]], [[4qlu]], [[4qlv]] - y20S core+ peptide inhibitor<br />
**[[5cz6]], [[5cz7]] - y20S (mutant) + peptide inhibitor<br />
**[[3h6f]], [[3h6i]], [[3hf9]], [[2fhh]], [[3krd]] – Mt20S core+inhibitor<br />
**[[3nzj]], [[3nzw]], [[3nzx]] - y20S + TMC-95A mimic ligand<br />
**[[4qvl]], [[4qw4]], [[4z1l]], [[3tdd]], [[4j70]] – y20S + cancer drug<br />
**[[4qvm]], [[4qvn]], [[4qvp]], [[4qvq]], [[4qvv]], [[4qvw]], [[4qvy]], [[4qw0]], [[4qw1]], [[4qw3]], [[4qw5]], [[4qw6]], [[4qw7]], [[4qwf]], [[4qwg]], [[4qwi]], [[4qwj]], [[4qwk]], [[4qwl]], [[4qwr]], [[4qws]], [[4qwu]], [[5cz8]], [[5cz9]], [[5fgd]], [[5fge]], [[5fgf]], [[5fgg]], [[5fgi]], [[5fhs]], [[5d0z]], [[5d0x]], [[5d0v]], [[5d0s]], [[5cz5]], [[5bxn]] - y20S (mutant) + cancer drug<br />
**[[4x6z]] - y20S + modulator<br />
**[[5gjq]] - y20S + ubiquitin carboxyl hydrolase 14 + polyubiquitin<br />
**[[5l5a]] - y20S + h20S beta5i<br />
**[[5ltt]]  - y20S + h20S beta5i + inhibitor<br />
**[[5l5b]], [[5l5r]] - y20S + h20S beta5i + h20S beta6<br />
**[[5l5w]] - y20S + h20S beta5c + h20S beta6<br />
**[[5l5x]], [[5l60]], [[5l61]] - y20S + h20S beta5c + h20S beta6 + inhibitor<br />
**[[5l5y]], [[5l5z]] - y20S + h20S beta5c + h20S beta6 + cancer drug<br />
**[[5l5d]], [[5l5h]], [[5l5q]], [[5l5i]], [[5l5j]], [[5l5o]], [[5l5p]], [[5l5s]], [[5l5t]], [[5l5u]], [[5l5v]], [[5l62]], [[5l63]], [[5l64]], [[5l68]], [[5l69]], [[5l6a]], [[5l6c]], [[5m2b]] - y20S + h20S beta5i + h20S beta6 + inhibitor<br />
**[[5l5e]], [[5l5f]] - y20S + h20S beta5i + h20S beta6 + cancer drug<br />
**[[5l65]], [[5l66]] - y20S + m20S beta5i + m20S beta6 + cancer drug<br />
**[[5l67]], [[5l6b]] - y20S + m20S beta5i + m20S beta6 + inhibitor<br />
**[[5fmg]] - Pf20S + inhibitor - ''Plasmodium falciparum'' - Cryo EM<br />
**[[5trr]], [[5trs]], [[5try]], [[5ts0]], [[5tho]], [[5trg]] - Mt20S + peptide<br />
* Proteasome partial 20S particle
**[[2kqz]], [[2kr0]] – hPRTS ubiquitin receptor domain<br />
**[[2ku1]], [[2ku2]] – Taa-PRTS chains A-G <br />
**[[3fp9]] – MtATPase chains A-L<br />
**[[1j2p]] – AfPRTS α subunit<br />
**[[2jay]] – MtPRTS β subunit<br />
**[[5nyw]] – PRTS β subunit – ''Yersinia bercovieri''<br />
*Proteasome partial 26S particle
**[[5l4k]] - hPRTS lid - CryoEM<br />
**[[5dsv]] - hPRTS subunit a type-3<br />
**[[1p9c]] – hPRTS subunit 4 C-terminal<br />
**[[1p9d]] - hPRTS subunit 4 C-terminal + HHR23A ubiquitin-like domain<br />
**[[1uel]] - hPRTS subunit 4 C-terminal + HHR23A ubiquitin-like domain - NMR<br />
**[[1yx4]] - hPRTS subunit 4 – NMR<br />
**[[1yx5]], [[1yx6]], [[2kde]], [[2kdf]] - hPRTS subunit 4+ubiquitin – NMR<br />
**[[2o95]], [[2o96]] - hPRTS subunit 7<br />
**[[3kw6]] - hPRTS subunit 8<br />
**[[2krk]] - hPRTS subunit 8 – NMR<br />
**[[1qym]], [[1uoh]] - hPRTS subunit 10<br />
**[[1tr4]] - hPRTS subunit 10 – NMR<br />
**[[4nik]] - hPRTS subunit 10 + single-chain Fv<br />
**[[3t5x]] - hPRTS subunit Dss1 + PCI domain-containing protein 2<br />
**[[2dvw]], [[2dwz]] - mPRTS subunit 10 + hPRTS subunit 6B – mouse<br />
**[[3aji]] - mPRTS subunit 10 +  subunit 4<br />
**[[2z59]] - mPRTS subunit RPN13+ubiquitin<br />
**[[2x5n]] - PRTS subunit RPN10 VWA domain – fission yeast<br />
**[[5ln1]] - yPRTS subunit RPN10 + polyubiquitin<br />
**[[4ady]] - yPRTS subunit RPN2<br />
**[[3vlf]] - yPRTS subunit 7 + DNA mismatch repair protein<br />
**[[2mr3]] - yPRTS subunit RPN9 – NMR<br />
**[[2mqw]] - yPRTS subunit RPN9 N terminal – NMR<br />
**[[2mri]] - yPRTS subunit RPN9 C terminal – NMR<br />
**[[4b0z]] - yPRTS subunit RPN12<br />
**[[2z4d]] - yPRTS subunit RPN13<br />
**[[3vl1]] - yPRTS subunit RPN14 (mutant)<br />
**[[4o8x]], [[4o8y]], [[5w83]], [[4owp]] - yPRTS subunit RPN8 + RPN11<br />
**[[4ocl]], [[4ocm]], [[4ocn]] - yPRTS subunit RPN8 + RPN11 + nanobody<br />
**[[5u4p]] - yPRTS subunit RPN8 + RPN11 + S31<br />
**[[3t5v]], [[5l3t]], [[5g5p]], [[4trq]] - yPRTS subunit SEM1 + nuclear mRNA export proteins SAC3 and THP1<br /
**[[3txm]], [[3txn]] – PRTS subunit P42B – ''Drosophila melanogaster''<br />
**[[5ubp]] - yPRTS subunit SEM1 + nuclear mRNA export protein THP1 + leucine permease transcriptional regulator<br />
*Proteasome 26S particle
**[[5l4g]], [[5gjr]], [[5ln3]], [[5t0c]], [[5t0g]], [[5t0h]], [[5t0i]], [[5t0j]], [[5vhs]], [[5vhr]], [[5vhq]], [[5vhp]], [[5vho]], [[5vhn]], [[5vhm]], [[5vhj]], [[5vhi]], [[5vhh]], [[5vhf]], [[5vgz]], [[5vft]], [[5vfr]], [[5vfo]] - hPRTS - Cryo EM<br />
**[[5m32]] - hPRTS + inhibitor - Cryo EM<br />
**[[6epf]], [[6epe]], [[6epd]], [[6epc]] – PRTS – rat - Cryo EM<br />
**[[3j47]], [[4cr2]], [[4cr3]], [[4cr4]], [[5wvi]], [[5mpc]] – yPRTS – Cryo EM<br />
**[[5wvk]] - yPRTS + ADP - Cryo EM<br />
**[[5mp9]], [[5mpa]], [[5mpd]], [[5mpe]] - yPRTS + ATP - Cryo EM<br />
**[[5mpb]] - yPRTS + AMPPNP - Cryo EM<br />
**[[4g4s]] – yPRTS + proteasome assembly chaperon 1 & 2<br />
**[[5a5b]] - yPRTS + UBP6 - Cryo EM<br />


}}
== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Latest revision as of 10:19, 23 July 2024

Function

Proteasome (PRTS) are large protein complexes which degrade unneeded proteins into small polypeptides[1]. The 26S PRTS is composed of a central 20S core particle which contains 4 stacked rings each with several members and two 19S caps. The 19S cap is composed of a base with 10 proteins six of which are ATPases and a lid which contains 9 proteins which bind polyubiquitin.

  • 13S PRTS is a PRTS core intermediate containing α ring, partial β ring and 3 chaperones[2].
  • 15S PRTS is half of an 20S PRTS and upon dimerisation forms the mature 20S PRTS[3].

For more details see 3unb.

Structural highlights

The core particle two outer rings contain 7 α subunits (Y7, Y13, PRE6, PRE5, PUP2, C1, C7-α) which form the PRTS gate. The two inner rings contain 7 β subunits (PRE2, PRE4, PRE3, PUP1, PUP3, C5, C11) with protease activity[4].

  • .
  • of chain H.
  • .

3D Structures of Proteasome

Proteasome 3D structures

See Also

PROTAC (Proteolysis-Targeting Chimera), an alternative to conventional enzyme inhibitors, by enabling proteasome induced degradation of the target protein.

Yeast proteasome 20S core complex with salinosporamide derivative, 3gpt

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Saeki Y, Tanaka K. Assembly and function of the proteasome. Methods Mol Biol. 2012;832:315-37. doi: 10.1007/978-1-61779-474-2_22. PMID:22350895 doi:http://dx.doi.org/10.1007/978-1-61779-474-2_22
  2. ↑ Schnell HM, Walsh RM Jr, Rawson S, Kaur M, Bhanu MK, Tian G, Prado MA, Guerra-Moreno A, Paulo JA, Gygi SP, Roelofs J, Finley D, Hanna J. Structures of chaperone-associated assembly intermediates reveal coordinated mechanisms of proteasome biogenesis. Nat Struct Mol Biol. 2021 May;28(5):418-425. PMID:33846632 doi:10.1038/s41594-021-00583-9
  3. ↑ Tundo GR, Sbardella D, Santoro AM, Coletta A, Oddone F, Grasso G, Milardi D, Lacal PM, Marini S, Purrello R, Graziani G, Coletta M. The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges. Pharmacol Ther. 2020 Sep;213:107579. PMID:32442437 doi:10.1016/j.pharmthera.2020.107579
  4. ↑ Coux O, Tanaka K, Goldberg AL. Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem. 1996;65:801-47. PMID:8811196 doi:http://dx.doi.org/10.1146/annurev.bi.65.070196.004101

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