Molecular architecture of the PBP2-MreC core bacterial cell wall synthesis complex

Author(s)

Contreras-Martel, Carlos ^[1] ; Martins, Alexandre ^[1] ; Ecobichon, Chantal ^{[2, 3]} ; Trindade, Daniel Maragno ^[4] ; Mattei, Pierre-Jean ^[1] ; Hicham, Samia ^{[2, 3]} ; Hardouin, Pierre ^[1] ; El Ghachi, Meriem ^{[2, 3]} ; Boneca, Ivo G. ^{[2, 3]} ; Dessen, Andrea ^{[1, 4]}

Affiliation

^[1] Univ Grenoble Alpes, CNRS, CEA, IBS, Bacterial Pathogenesis Grp, F-38000 Grenoble - France

^[2] Inst Pasteur, Unit Biol & Genet Bacterial Cell Wall, F-75015 Paris - France

^[3] INSERM, Grp Avenir, F-75015 Paris - France

^[4] CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13084971 Campinas, SP - Brazil

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 8, OCT 3 2017.
• Web of Science Citations: 9

Abstract

Bacterial cell wall biosynthesis is an essential process that requires the coordinated activity of peptidoglycan biosynthesis enzymes within multi-protein complexes involved in cell division (the ``divisome{''}) and lateral wall growth (the ``elongasome{''}). MreC is a structural protein that serves as a platform during wall elongation, scaffolding other essential peptidoglycan biosynthesis macromolecules, such as penicillin-binding proteins. Despite the importance of these multi-partite complexes, details of their architecture have remained elusive due to the transitory nature of their interactions. Here, we present the crystal structures of the soluble PBP2: MreC core elongasome complex from Helicobacter pylori, and of uncomplexed PBP2. PBP2 recognizes the two-winged MreC molecule upon opening of its N-terminal region, revealing a hydrophobic zipper that serves as binding platform. The PBP2: MreC interface is essential both for protein recognition in vitro and maintenance of bacterial shape and growth. This work allows visualization as to how peptidoglycan machinery proteins are scaffolded, revealing interaction regions that could be targeted by tailored inhibitors. (AU)

• FAPESP's process: 11/52067-6 - Assembly and structure of macromolecular complexes involved in bacterial cell wall: biosynthesis and virulence
• Grantee: Andrea Dessen de Souza e Silva
• Support Opportunities: Research Projects - SPEC Program