8EC6

Cryo-EM structure of the Glutaminase C core filament (fGAC)

8EC6 の概要

• エントリーDOI: 10.2210/pdb8ec6/pdb
• EMDBエントリー: 28013
• 分子名称: Isoform 2 of Glutaminase kidney isoform, mitochondrial, PHOSPHATE ION (2 entities in total)
• 機能のキーワード: mitochondria, filament, hydrolase
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 427375.46

構造登録者

Ambrosio, A.L.,Dias, S.M.,Quesnay, J.E.,Portugal, R.V.,Cassago, A.,van Heel, M.G.,Islam, Z.,Rodrigues, C.T. (登録日: 2022-09-01, 公開日: 2023-09-20, 最終更新日: 2023-12-27)

主引用文献

Adamoski, D.,Dias, M.M.,Quesnay, J.E.N.,Yang, Z.,Zagoriy, I.,Steyer, A.M.,Rodrigues, C.T.,da Silva Bastos, A.C.,da Silva, B.N.,Costa, R.K.E.,de Abreu, F.M.O.,Islam, Z.,Cassago, A.,van Heel, M.G.,Consonni, S.R.,Mattei, S.,Mahamid, J.,Portugal, R.V.,Ambrosio, A.L.B.,Dias, S.M.G.
Molecular mechanism of glutaminase activation through filamentation and the role of filaments in mitophagy protection.
Nat.Struct.Mol.Biol., 30:1902-1912, 2023

PubMed Abstract: 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.

PubMed: 37857822
DOI: 10.1038/s41594-023-01118-0

実験手法

ELECTRON MICROSCOPY (3.1 Å)