3D architecture and structural flexibility revealed in the subfamily of large glutamate dehydrogenases by a mycobacterial enzyme

DOI: 10.1038/s42003-021-02222-x

Authors: Melisa Lazaro (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Roberto Melero (Centro Nacional de Biotecnología, CNB-CSIC) , Charlotte Huet (Institut Pasteur, CNRS UMR 3528, Université de Paris) , Jorge Lopez-Alonso (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Sandra Delgado (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Alexandra Dodu (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Eduardo M. Bruch (Integrated Structural Biology Department, IGBMC) , Luciano A. Abriata (École Polytechnique Fédérale de Lausanne) , Pedro M. Alzari (Institut Pasteur, CNRS UMR 3528, Université de Paris) , Mikel Valle (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , María-Natalia Lisa (Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR); Plataforma de Biología Estructural y Metabolómica (PLABEM); nstitut Pasteur, CNRS UMR 3528, Université de Paris)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Communications Biology , VOL 4

State: Published (Approved)
Published: June 2021
Diamond Proposal Number(s): 14743

Abstract: Glutamate dehydrogenases (GDHs) are widespread metabolic enzymes that play key roles in nitrogen homeostasis. Large glutamate dehydrogenases composed of 180 kDa subunits (L-GDHs180) contain long N- and C-terminal segments flanking the catalytic core. Despite the relevance of L-GDHs180 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-GDH180 (mL-GDH180) adopts a quaternary structure that is radically different from that of related low molecular weight enzymes. Intersubunit contacts in mL-GDH180 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.

Journal Keywords: Cryoelectron microscopy; Pathogens; X-ray crystallography

Diamond Keywords: Enzymes; Bacteria

Subject Areas: Biology and Bio-materials, Chemistry

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios II-Titan Krios II at Diamond

Added On: 09/06/2021 10:24

Documents:
s42003-021-02222-x.pdf

Discipline Tags:

Pathogens Health & Wellbeing Catalysis Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)