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{{STRUCTURE_3gpt|  PDB=3gpt  | SIZE=400| SCENE= |right|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 ==
[[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]].


[[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 core particle two outer rings contain 7 α subunits which form the PRTS gate.  The two inner rings contain 6 β subunits with protease activity. 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 />
== Structural highlights ==
For more details see [[3unb]].
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<ref>PMID:8811196</ref>.  
*<scene name='41/417543/Cv/2'>α subunits and β subunits</scene>.
*<scene name='41/417543/Cv/6'>Salinosporamide derivative binding site</scene> of chain H.
*<scene name='41/417543/Cv/7'>Covalent bond between Salinosporamide derivative and Thr1</scene>.


== 3D Structures of Proteasome ==
== 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.
</StructureSection>


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|
* Proteasome 20S particle
**[[3mfe]], [[3mi0]], [[2fhg]] – Mt20S core – ''Mycobacterium tuberculosis''<br />
**[[3gpt]], [[3gpw]], [[1g0u]] – y20S core - yeast<br />
**[[1ryp]], [[3wxr]], [[4qux]], [[4quy]], [[4qv0]], [[4qv1]], [[4qv3]], [[4qv4]], [[4qv5]], [[4qv6]], [[4qv7]], [[4qv8]], [[4qv9]] - y20S core (mutant)<br />
**[[4r3o]] – h20S – human<br />
**[[3mka]], [[3hfa]] – Mt20S core (mutant)<br />
**[[3c91]], [[3c92]], [[1pma]], [[3j9i]] – Ta20S core - ''Themoplasma acidophilum''<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 />
**[[1iru]] – 20S core - bovine<br />
**[[3une]] – m20S core – mouse<br />
**[[3unh]] – m20S core (immuno)
*Proteasome 20S+activator protein
**[[1vsy]], [[3l5q]] – 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 />
*Proteasome 20S+inhibitor
**[[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]] – y20S core+inhibitor<br />
**[[4qxj]], [[4qz0]], [[4qz1]], [[4qz2]], [[4qz3]], [[4qz4]], [[4qz5]], [[4qz6]], [[4qz7]], [[4qzw]], [[4qzx]], [[4r00]], [[4r02]]  – y20S (mutant) + inhibitor<br />
**[[3tdd]], [[4j70]] - y20S core + belactosin<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 />
**[[3h6f]], [[3h6i]], [[3hf9]], [[2fhh]], [[3krd]] – Mt20S core+inhibitor<br />
**[[3nzj]], [[3nzw]], [[3nzx]] - y20S + TMC-95A mimic ligand<br />
**[[2zcy]] – y20S+syringolin<br />
**[[4qvl]], [[4qw4]] – y20S + lymphoma drug<br />
**[[4qvm]], [[4qvn]], [[4qvp]], [[4qvq]], [[4qvv]], [[4qvw]], [[4qvy]], [[4qw0]], [[4qw1]], [[4qw3]], [[4qw5]], [[4qw6]], [[4qw7]], [[4qwf]], [[4qwg]], [[4qwi]], [[4qwj]], [[4qwk]], [[4qwl]], [[4qwr]], [[4qws]], [[4qwu]] – y20S (mutant) + lymphoma drug<br />
**[[4r67]] – h20S + cancer drug<br />
**[[3unb]], [[3unf]] – m20S + inhibitor
* Proteasome partial 20S particle
**[[2ku1]], [[2ku2]] – Taa-PRTS chains A-G <br />
**[[3fp9]] – MtATPase chains A-L<br />
**[[1j2p]] – Af α subunit<br />
**[[2jay]] – Mt β subunit<br />
**[[2kqz]], [[2kr0]] – hPRTS ubiquitin receptor domain
*Proteasome partial 26S particle
**[[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 />
**[[2x5n]] - PRTS subunit RPN10 VWA domain – fission yeast<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]] - yPRTS subunit RPN8 + RPN11<br />
**[[4ocl]], [[4ocm]], [[4ocn]] - yPRTS subunit RPN8 + RPN11 + nanobody<br />
**[[3t5v]] - yPRTS subunit SEM1 + nuclear mRNA export proteins SAC3 and THP1<br />
**[[2z59]] - mPRTS subunit RPN13+ubiquitin<br />
**[[3txm]], [[3txn]] – PRTS subunit P42B – ''Drosophila melanogaster''
*Proteasome 26S particle
**[[4b4t]], [[3j47]], [[4cr2]], [[4cr3]], [[4cr4]] – yPRTS – Cryo EM<br />
**[[4g4s]] – yPRTS + proteasome assembly chaperon 1 & 2<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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