Proteasome
From Proteopedia
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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]]'> | ||
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== 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 == | ||
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| - | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
| - | {{#tree:id=OrganizedByTopic|openlevels=0| | ||
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| - | * Proteasome 20S core | ||
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| - | **[[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 /> | ||
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| - | *Proteasome 20S+activator protein | ||
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| - | **[[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 /> | ||
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| - | *Proteasome 20S+inhibitor | ||
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| - | **[[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 /> | ||
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| - | * Proteasome partial 20S particle | ||
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| - | **[[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 /> | ||
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| - | *Proteasome partial 26S particle | ||
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| - | **[[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 /> | ||
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| - | *Proteasome 26S particle | ||
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| - | **[[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]] | ||
Current revision
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References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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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