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Proteasome
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| - | <StructureSection load=' | + | <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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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>. | 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/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>. | ||
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| + | == 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> | </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 particle | ||
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| - | **[[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) | ||
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| - | *Proteasome 20S+activator protein | ||
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| - | **[[4v7o]] – 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 /> | ||
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| - | *Proteasome 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]], [[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 | ||
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| - | * Proteasome partial 20S particle | ||
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| - | **[[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 | ||
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| - | *Proteasome partial 26S particle | ||
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| - | **[[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'' | ||
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| - | *Proteasome 26S particle | ||
| - | **[[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]] | ||
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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