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Proteasome

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[[Image:3gpt.jpg|left|200px|thumb|Crystal Structure of Proteasome, [[3gpt]]]]
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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]]'>
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{{STRUCTURE_3gpt| PDB=3gpt | SIZE=400| SCENE= |right|CAPTION=Proteasome complex with salinosporamide derivative, [[3gpt]] }}
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== Function ==
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[[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 />
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*'''13S PRTS''' is a PRTS core intermediate containing α ring, partial β ring and 3 chaperones<ref>PMID:33846632</ref>.
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*'''15S PRTS''' is half of an 20S PRTS and upon dimerisation forms the mature 20S PRTS<ref>PMID:32442437</ref>.
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For more details see [[3unb]].
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== Structural highlights ==
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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>.
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*<scene name='41/417543/Cv/2'>α subunits and β subunits</scene>.
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*<scene name='41/417543/Cv/6'>Salinosporamide derivative binding site</scene> of chain H.
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*<scene name='41/417543/Cv/7'>Covalent bond between Salinosporamide derivative and Thr1</scene>.
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[[Proteasome]] (PRTS) are large protein complexes which degrade unneeded proteins into small polypeptides. 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. The images at the left and at the right correspond to one representative Proteasome, ''i.e.'' the crystal structure of yeast Proteasome ([[3gpt]]).
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{{TOC limit|limit=2}}
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== 3D Structures of Proteasome ==
== 3D Structures of Proteasome ==
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[[Proteasome 3D structures]]
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== See Also ==
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[[PROTAC]] (Proteolysis-Targeting Chimera), an alternative to conventional enzyme inhibitors, by enabling proteasome induced degradation of the target protein.
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</StructureSection>
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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== References ==
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<references/>
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=== 20S particle ===
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[[3mfe]], [[3mi0]], [[2fhg]] – Mt20S core – ''Mycobacterium tuberculosis''<br />
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[[3gpt]], [[3gpw]], [[1g0u]] – y20S core - yeast<br />
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[[1ryp]] - y20S core (mutant)<br />
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[[2zcy]] – y20S+syringolin<br />
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[[3mka]], [[3hfa]] – Mt20S core (mutant)<br />
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[[3c91]], [[3c92]], [[1pma]] – Ta20S core - ''Themoplasma acidophilum''<br />
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[[3h4p]] – 20S core – ''Methanocaldococcus janaschii''<br />
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[[2h6j]], [[1q5r]] – Re20S core (mutant) – ''Rhodococcus erythropolis''<br />
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[[1q5q]] - Re20S core<br />
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[[1j2q]] – Af20S core - ''Archaeoglobus fulgidus''<br />
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[[1iru]] – 20S core - bovine<br />
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[[3une]] – m20S core – mouse<br />
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[[3unh]] – m20S core (immuno)
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=== 20S+activator protein ===
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[[1vsy]], [[1l5q]] – y20S core+ Blm10 <br />
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[[1z7q]], [[1fnt]] – y20S core+PA26<br />
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[[3ipm]], [[3jrm]], [[3jse]], [[3jtl]], [[1ya7]], [[1yar]], [[1yau]] - Taa-PRTS chains A-G+ Tab-PRTS chains H-N+PA26 chains O-U <br />
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=== 20S+inhibitor ===
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[[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]] – y20S core+inhibitor<br />
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[[3tdd]], [[4j70]] - y20S core + belactosin<br />
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[[3h6f]], [[3h6i]], [[3hf9]], [[2fhh]], [[3krd]] – Mt20S core+inhibitor<br />
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[[3nzj]], [[3nzw]], [[3nzx]] - y20S + TMC-95A mimic ligand<br />
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[[3unb]], [[3unf]] – m20S + inhibitor
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=== Partial 20S ===
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[[2ku1]], [[2ku2]] – Taa-PRTS chains A-G <br />
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[[3fp9]] – MtATPase chains A-L<br />
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[[1j2p]] – Af α subunit<br />
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[[2jay]] – Mt β subunit<br />
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[[2kqz]], [[2kr0]] – hPRTS ubiquitin receptor domain
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===Partial 26S===
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[[1p9c]] – hPRTS subunit 4 C-terminal – human<br />
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[[1p9d]] - hPRTS subunit 4 C-terminal + HHR23A ubiquitin-like domain<br />
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[[1uel]] - hPRTS subunit 4 C-terminal + HHR23A ubiquitin-like domain - NMR<br />
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[[1yx4]] - hPRTS subunit 4 – NMR<br />
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[[1yx5]], [[1yx6]], [[2kde]], [[2kdf]] - hPRTS subunit 4+ubiquitin – NMR<br />
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[[2o95]], [[2o96]] - hPRTS subunit 7<br />
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[[3kw6]] - hPRTS subunit 8<br />
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[[2krk]] - hPRTS subunit 8 – NMR<br />
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[[1qym]], [[1uoh]] - hPRTS subunit 10<br />
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[[1tr4]] - hPRTS subunit 10 – NMR<br />
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[[3t5x]] - hPRTS subunit Dss1 + PCI domain-containing protein 2<br />
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[[2dvw]], [[2dwz]] - mPRTS subunit 10 + hPRTS subunit 6B – mouse<br />
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[[3aji]] - mPRTS subunit 10 + subunit 4<br />
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[[2x5n]] - PRTS subunit RPN10 VWA domain – fission yeast<br />
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[[4ady]] - yPRTS subunit RPN2<br />
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[[3vlf]] - yPRTS subunit 7 + DNA mismatch repair protein<br />
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[[4b0z]] - yPRTS subunit RPN12<br />
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[[2z4d]] - yPRTS subunit RPN13<br />
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[[3vl1]] - yPRTS subunit RPN14 (mutant)<br />
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[[2z59]] - mPRTS subunit RPN13+ubiquitin<br />
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[[3txm]], [[3txn]] – PRTS subunit P42B – ''Drosophila melanogaster''
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===26S===
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[[4b4t]] – yPRTS – Cryo EM
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[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

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

Drag the structure with the mouse to rotate

References

  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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