+検索条件
-Structure paper
タイトル | Molecular mechanism of glutaminase activation through filamentation and the role of filaments in mitophagy protection. |
---|---|
ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 30, Issue 12, Page 1902-1912, Year 2023 |
掲載日 | 2023年10月19日 |
著者 | Douglas Adamoski / Marilia Meira Dias / Jose Edwin Neciosup Quesñay / Zhengyi Yang / Ievgeniia Zagoriy / Anna M Steyer / Camila Tanimoto Rodrigues / Alliny Cristiny da Silva Bastos / Bianca Novaes da Silva / Renna Karoline Eloi Costa / Flávia Mayumi Odahara de Abreu / Zeyaul Islam / Alexandre Cassago / Marin Gerard van Heel / Sílvio Roberto Consonni / Simone Mattei / Julia Mahamid / Rodrigo Villares Portugal / Andre Luis Berteli Ambrosio / Sandra Martha Gomes Dias / |
PubMed 要旨 | Glutaminase (GLS), which deaminates glutamine to form glutamate, is a mitochondrial tetrameric protein complex. Although inorganic phosphate (Pi) is known to promote GLS filamentation and activation, ...Glutaminase (GLS), which deaminates glutamine to form glutamate, is a mitochondrial tetrameric protein complex. Although inorganic phosphate (Pi) is known to promote GLS filamentation and activation, the molecular basis of this mechanism is unknown. Here we aimed to determine the molecular mechanism of Pi-induced mouse GLS filamentation and its impact on mitochondrial physiology. Single-particle cryogenic electron microscopy revealed an allosteric mechanism in which Pi binding at the tetramer interface and the activation loop is coupled to direct nucleophile activation at the active site. The active conformation is prone to enzyme filamentation. Notably, human GLS filaments form inside tubulated mitochondria following glutamine withdrawal, as shown by in situ cryo-electron tomography of cells thinned by cryo-focused ion beam milling. Mitochondria with GLS filaments exhibit increased protection from mitophagy. We reveal roles of filamentous GLS in mitochondrial morphology and recycling. |
リンク | Nat Struct Mol Biol / PubMed:37857822 |
手法 | EM (単粒子) |
解像度 | 3.1 Å |
構造データ | EMDB-28013, PDB-8ec6: |
化合物 | ChemComp-PO4: |
由来 |
|
キーワード | HYDROLASE / Mitochondria / Filament |