Structural highlights
Disease
PSMG2_HUMAN The disease may be caused by variants affecting the gene represented in this entry.
Function
PSMG2_HUMAN Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG1. The PSMG1-PSMG2 heterodimer binds to the PSMA5 and PSMA7 proteasome subunits, promotes assembly of the proteasome alpha subunits into the heteroheptameric alpha ring and prevents alpha ring dimerization.[1] [2]
Publication Abstract from PubMed
Dedicated assembly factors orchestrate the stepwise production of many molecular machines, including the 28-subunit proteasome core particle (CP) that mediates protein degradation. Here we report cryo-electron microscopy reconstructions of seven recombinant human subcomplexes that visualize all five chaperones and the three active site propeptides across a wide swath of the assembly pathway. Comparison of these chaperone-bound intermediates and a matching mature CP reveals molecular mechanisms determining the order of successive subunit additions, as well as how proteasome subcomplexes and assembly factors structurally adapt upon progressive subunit incorporation to stabilize intermediates, facilitate the formation of subsequent intermediates and ultimately rearrange to coordinate proteolytic activation with gated access to active sites. This work establishes a methodologic approach for structural analysis of multiprotein complex assembly intermediates, illuminates specific functions of assembly factors and reveals conceptual principles underlying human proteasome biogenesis, thus providing an explanation for many previous biochemical and genetic observations.
Visualizing chaperone-mediated multistep assembly of the human 20S proteasome.,Adolf F, Du J, Goodall EA, Walsh RM Jr, Rawson S, von Gronau S, Harper JW, Hanna J, Schulman BA Nat Struct Mol Biol. 2024 Aug;31(8):1176-1188. doi: 10.1038/s41594-024-01268-9. , Epub 2024 Apr 10. PMID:38600324[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hirano Y, Hendil KB, Yashiroda H, Iemura S, Nagane R, Hioki Y, Natsume T, Tanaka K, Murata S. A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes. Nature. 2005 Oct 27;437(7063):1381-5. PMID:16251969 doi:10.1038/nature04106
- ↑ Le Tallec B, Barrault MB, Courbeyrette R, Guerois R, Marsolier-Kergoat MC, Peyroche A. 20S proteasome assembly is orchestrated by two distinct pairs of chaperones in yeast and in mammals. Mol Cell. 2007 Aug 17;27(4):660-74. PMID:17707236 doi:10.1016/j.molcel.2007.06.025
- ↑ Adolf F, Du J, Goodall EA, Walsh RM Jr, Rawson S, von Gronau S, Harper JW, Hanna J, Schulman BA. Visualizing chaperone-mediated multistep assembly of the human 20S proteasome. Nat Struct Mol Biol. 2024 Aug;31(8):1176-1188. PMID:38600324 doi:10.1038/s41594-024-01268-9
