%0 Journal Article %T 3D architecture and structural flexibility revealed in the subfamily of large glutamate dehydrogenases by a mycobacterial enzyme %+ Basque Research and Technology Alliance (BRTA) %+ Centro Nacional de Biotecnología [Madrid] (CNB-CSIC) %+ Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)) %+ Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) %+ Ecole Polytechnique Fédérale de Lausanne (EPFL) %+ Instituto de Biología Molecular y Celular de Rosario [Rosario] (IBR) %+ Plataforma de Biología Estructural y Metabolómica [Rosario] (PLABEM) %A Lázaro, Melisa %A Melero, Roberto %A Huet, Charlotte %A López-Alonso, Jorge, P %A Delgado, Sandra %A Dodu, Alexandra %A Bruch, Eduardo, M %A Abriata, Luciano, A %A Alzari, Pedro, M %A Valle, Mikel %A Lisa, María-Natalia %Z This work was supported by the grant PICT 2017-1932, from the Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (Agencia I + D + i, Argentina), received by M.N.L., and the grant PGC2018-098996-B-100 from the Spanish Ministerio de Ciencia e Innovación, received by M.V.; M.V. thanks the AEI (Agencia Estatal de Investigación) for the Severo Ochoa Excellence Accreditation (SEV-2016-0644). %< avec comité de lecture %@ 2399-3642 %J Communications Biology %I Nature Publishing Group %V 4 %N 1 %P 684 %8 2021-06 %D 2021 %R 10.1038/s42003-021-02222-x %M 34083757 %Z Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] %Z Life Sciences [q-bio]/Microbiology and Parasitology/BacteriologyJournal articles %X Glutamate dehydrogenases (GDHs) are widespread metabolic enzymes that play key roles in nitrogen homeostasis. Large glutamate dehydrogenases composed of 180 kDa subunits (L-GDHs 180) contain long N-and C-terminal segments flanking the catalytic core. Despite the relevance of L-GDHs 180 in bacterial physiology, the lack of structural data for these enzymes has limited the progress of functional studies. Here we show that the mycobacterial L-GDH 180 (mL-GDH 180) adopts a quaternary structure that is radically different from that of related low molecular weight enzymes. Intersubunit contacts in mL-GDH 180 involve a C-terminal domain that we propose as a new fold and a flexible N-terminal segment comprising ACT-like and PAS-type domains that could act as metabolic sensors for allosteric regulation. These findings uncover unique aspects of the structure-function relationship in the subfamily of L-GDHs. %G English %2 https://hal.science/hal-03878750/document %2 https://hal.science/hal-03878750/file/s42003-021-02222-x.pdf %L hal-03878750 %U https://hal.science/hal-03878750 %~ INSERM %~ PASTEUR %~ CNRS %~ IGBMC %~ UNIV-STRASBG %~ SITE-ALSACE %~ UNIV-PARIS %~ UNIVERSITE-PARIS