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-Structure paper
タイトル | Identification of a depupylation regulator for an essential enzyme in . |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 121, Issue 49, Page e2407239121, Year 2024 |
掲載日 | 2024年12月3日 |
著者 | Shoshanna C Kahne / Jin Hee Yoo / James Chen / Kehilwe Nakedi / Lakshminarayan M Iyer / Gregory Putzel / Nora M Samhadaneh / Alejandro Pironti / L Aravind / Damian C Ekiert / Gira Bhabha / Kyu Y Rhee / K Heran Darwin / |
PubMed 要旨 | In , proteins that are posttranslationally modified with a prokaryotic ubiquitin-like protein (Pup) can be degraded by bacterial proteasomes. A single Pup-ligase and depupylase shape the pupylome, ...In , proteins that are posttranslationally modified with a prokaryotic ubiquitin-like protein (Pup) can be degraded by bacterial proteasomes. A single Pup-ligase and depupylase shape the pupylome, but the mechanisms regulating their substrate specificity are incompletely understood. Here, we identified a depupylation regulator, a protein called CoaX, through its copurification with the depupylase Dop. CoaX is a pseudopantothenate kinase that showed evidence of binding to pantothenate, an essential nutrient synthesizes, but not its phosphorylation. In a ∆ mutant, pantothenate synthesis enzymes including PanB, a substrate of the Pup-proteasome system (PPS), were more abundant than in the parental strain. In vitro, CoaX specifically accelerated depupylation of Pup~PanB, while addition of pantothenate inhibited this reaction. In culture, media supplementation with pantothenate decreased PanB levels, which required CoaX. Collectively, we propose CoaX regulates PanB abundance in response to pantothenate levels by modulating its vulnerability to proteolysis by proteasomes. |
リンク | Proc Natl Acad Sci U S A / PubMed:39585979 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 1.98 - 2.71 Å |
構造データ | EMDB-44303, PDB-9b78: EMDB-44304, PDB-9b79: EMDB-45652: Complex of M. smegmatis Dop with M. tuberculosis CoaX and Pup91 (Local Refine Map of Dop-Pup91) EMDB-45653: Complex of M. smegmatis Dop with M. tuberculosis CoaX and Pup91 (Consensus Map) EMDB-45654: Complex of M. smegmatis Dop with M. tuberculosis CoaX and Pup91 (Composite Map) |
化合物 | ChemComp-HOH: |
由来 |
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キーワード | CYTOSOLIC PROTEIN / Pantothenate Kinase Isoform |