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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Alexander Berchansky, Michal Harel, Joel L. Sussman, Jaime Prilusky