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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The MurG glycosyltransferase provides an oligomeric scaffold for the cytoplasmic steps of peptidoglycan biosynthesis in the human pathogen Bordetella pertussis

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Laddomada, Federica [1] ; Miyachiro, Mayara M. [2, 3] ; Jessop, Matthew [1] ; Patin, Delphine [4, 5] ; Job, Viviana [1] ; Mengin-Lecreulx, Dominique [4, 5] ; Le Roy, Aline [1] ; Ebel, Christine [1] ; Breyton, Cecile [1] ; Gutsche, Irina [1] ; Dessen, Andrea [3, 1]
Total Authors: 11
[1] Univ Grenoble Alpes, CNRS, CEA, IBS, F-38000 Grenoble - France
[2] Univ Estadual Campinas UNICAMP, Dept Genet Evolucao & Bioagentes, Campinas, SP - Brazil
[3] CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13084971 Campinas, SP - Brazil
[4] Univ Paris Sud, CNRS, CEA, I2BC, F-91198 Gif Sur Yvette - France
[5] Univ Paris Saclay, F-91198 Gif Sur Yvette - France
Total Affiliations: 5
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 9, MAR 15 2019.
Web of Science Citations: 1

Peptidoglycan is a major component of the bacterial cell wall and thus a major determinant of cell shape. Its biosynthesis is initiated by several sequential reactions catalyzed by cytoplasmic Mur enzymes. Mur ligases (MurC, -D, -E, and -F) are essential for bacteria, metabolize molecules not present in eukaryotes, and are structurally and biochemically tractable. However, although many Mur inhibitors have been developed, few have shown promising antibacterial activity, prompting the hypothesis that within the cytoplasm, Mur enzymes could exist as a complex whose architecture limits access of small molecules to their active sites. This suggestion is supported by the observation that in many bacteria, mur genes are present in a single operon, and pairs of these genes often are fused to generate a single polypeptide. Here, we explored this genetic arrangement in the human pathogen Bordetella pertussis and show that MurE and MurF are expressed as a single, bifunctional protein. EM, small angle X-ray scattering (SAXS), and analytical centrifugation (AUC) revealed that the MurE-MurF fusion displays an elongated, flexible structure that can dimerize. Moreover, MurE-MurF interacted with the peripheral glycosyltransferase MurG, which formed discrete oligomers resembling 4- or 5-armed stars in EM images. The oligomeric structure of MurG may allow it to play a bona fide scaffolding role for a potential Mur complex, facilitating the efficient conveyance of peptidoglycan-building blocks toward the inner membrane leaflet. Our findings shed light on the structural determinants of a peptidoglycan formation complex involving Mur enzymes in bacterial cell wall formation. (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
FAPESP's process: 13/02451-0 - Structural characterization of an essential protein complex in cell wall formation
Grantee:Mayara Mayele Miyachiro
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 17/12436-9 - ANTIBIO-BAC: exploring the bacterial cell wall as a target for novel antibiotherapies
Grantee:Andrea Dessen de Souza e Silva
Support Opportunities: Research Projects - SPEC Program