National Institutes of Health/National Cancer Institute (NIH/NCI)
1 ZIA BC011490
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35-GM149314
米国
引用
ジャーナル: bioRxiv / 年: 2024 タイトル: Structure of Blm10:13S proteasome intermediate reveals parallel assembly pathways for the proteasome core particle. 著者: Mandeep Kaur / Xiang Chen / Stella Y Lee / Tyler M Weaver / Bret D Freudenthal / Kylie J Walters / Jeroen Roelofs / 要旨: Proteasomes are formed by chaperone-assisted assembly of core particles (CPs) and regulatory particles (RPs). The CP chaperone dimer Pba1/Pba2 binds early to proteasome subunits, and is thought to be ...Proteasomes are formed by chaperone-assisted assembly of core particles (CPs) and regulatory particles (RPs). The CP chaperone dimer Pba1/Pba2 binds early to proteasome subunits, and is thought to be replaced by Blm10 to form Blm10:CP, which promotes ATP-independent degradation of disordered proteins. Here, we present evidence of distinct parallel assembly pathways for CP by solving five cryo-EM structures including a Blm10:13S pre-assembly intermediate. Our data conflict with the current model of Blm10 and Pba1/Pba2 sequential activity in a single assembly pathway, as we find their CP binding is mutually exclusive and both are present on early and late assembly intermediates. CP affinity for Pba1/Pba2 is reduced during maturation, promoting Pba1/Pba2 release. We find Blm10 undergoes no such affinity switch, suggesting this pathway predominantly yields mature Blm10-bound CP. Altogether, our findings conflict with the current paradigm of sequential CP binding to instead indicate parallel assembly pathways by Pba1/Pba2 and Blm10.