6jpt

Publication Abstract from PubMed

The 26S proteasome is critical for the selective degradation of proteins in eukaryotic cells. This enzyme complex is composed of approximately 70 subunits, including the structurally homologous proteins alpha1-alpha7, which combine to form heptameric rings. The correct arrangement of these alpha subunits is essential for the function of the proteasome, but their assembly does not occur autonomously. Assembly of the alpha subunit is assisted by several chaperones, including the PAC3-PAC4 heterodimer. In this study we showed that the PAC3-PAC4 heterodimer functions as a molecular matchmaker, stabilizing the alpha4-alpha5-alpha6 subcomplex during the assembly of the alpha-ring. We solved a 0.96-A atomic resolution crystal structure for a PAC3 homodimer which, in conjunction with nuclear magnetic resonance (NMR) data, highlighted the mobility of the loop comprised of residues 51 to 61. Based on these structural and dynamic data, we created a three-dimensional model of the PAC3-4/alpha4/alpha5/alpha6 quintet complex, and used this model to investigate the molecular and structural basis of the mechanism of proteasome alpha subunit assembly, as mediated by the PAC3-PAC4 heterodimeric chaperone. Our results provide a potential basis for the development of selective inhibitors against proteasome biogenesis.

Molecular and Structural Basis of the Proteasome alpha Subunit Assembly Mechanism Mediated by the Proteasome-Assembling Chaperone PAC3-PAC4 Heterodimer.,Satoh T, Yagi-Utsumi M, Okamoto K, Kurimoto E, Tanaka K, Kato K Int J Mol Sci. 2019 May 7;20(9). pii: ijms20092231. doi: 10.3390/ijms20092231. PMID:31067643^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.