4qby

Publication Abstract from PubMed

Two clusters of configurations of the main proteolytic subunit beta5 were identified by principal component analysis of crystal structures of the yeast proteasome core particle (yCP). The apo-cluster encompasses unliganded species and complexes with nonpeptidic ligands, and the pep-cluster comprises complexes with peptidic ligands. The murine constitutive CP structures conform to the yeast system, with the apo-form settled in the apo-cluster and the PR-957 (a peptidic ligand) complex in the pep-cluster. In striking contrast, the murine immune CP classifies into the pep-cluster in both the apo and the PR-957-liganded species. The two clusters differ essentially by multiple small structural changes and a domain motion enabling enclosure of the peptidic ligand and formation of specific hydrogen bonds in the pep-cluster. The immune CP species is in optimal peptide binding configuration also in its apo form. This favors productive ligand binding and may help to explain the generally increased functional activity of the immunoproteasome. Molecular dynamics simulations of the representative murine species are consistent with the experimentally observed configurations. A comparison of all 28 subunits of the unliganded species with the peptidic liganded forms demonstrates a greatly enhanced plasticity of beta5 and suggests specific signaling pathways to other subunits.

Differential global structural changes in the core particle of yeast and mouse proteasome induced by ligand binding.,Arciniega M, Beck P, Lange OF, Groll M, Huber R Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):9479-84. doi:, 10.1073/pnas.1408018111. Epub 2014 Jun 16. PMID:24979800^[1]

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