10GX

Yeast Blm10 apo Structure

Summary for 10GX

• Entry DOI: 10.2210/pdb10gx/pdb
• EMDB information: 75163
• Descriptor: Proteasome activator BLM10 (1 entity in total)
• Functional Keywords: proteasome regulator, protein binding
• Biological source: Saccharomyces cerevisiae
• Total number of polymer chains: 1
• Total formula weight: 249243.67

Authors

Walsh Jr, R.M.,Rawson, S.,Fermin Perez, E.,Venclovaite, U.,Hanna, J. (deposition date: 2026-01-19, release date: 2026-07-22, Last modification date: 2026-08-05)

Primary citation

Fung, D.,Rawson, S.,Walsh Jr., R.M.,Fermin Perez, E.,Venclovaite, U.,Rajakumar, T.,Velez, B.,Hanna, J.
Blm10 and PI31 comprise a failsafe mechanism for proteasome inhibition.
Proc.Natl.Acad.Sci.USA, 123:e2611708123-e2611708123, 2026

PubMed Abstract: Blm10 (PA200 in mammals) is an evolutionarily conserved regulator of the proteasome's core particle (CP), a barrel-shaped complex that houses six individual protease subunits. Despite decades of study, Blm10's function has remained unresolved. Here, we provide structural, biochemical, and genetic evidence that yeast Blm10 inhibits the proteasome and that it does so in cooperation with a second proteasome inhibitor, PI31 (also known as Fub1). Both proteins are highly enriched in CPs with abnormal subunit composition, suggesting that Blm10 and PI31 may function to neutralize aberrant proteasomes. We report an unexpected proteasome configuration in which Blm10's dome-like structure completely encases PI31's N-terminal domain, which sits outside and atop the CP, while PI31's C-terminal domain is present inside the CP, simultaneously inhibiting all six active sites. These Blm10/PI31-bound CP are strongly deficient in degradation of both proteins and small peptides, and loss of both proteins results in strongly synergistic genetic phenotypes in vivo. These data suggest that Blm10 and PI31 constitute a partially redundant failsafe system for proteasome inhibition.

PubMed: 42485378
DOI: 10.1073/pnas.2611708123

Experimental method

ELECTRON MICROSCOPY (3.2 Å)