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Outer-membrane lipoprotein LpoB spans the periplasm to stimulate the peptidoglycan synthase PBP1B

Lookup NU author(s): Dr Alexander Egan, Dr Jacob BiboyORCiD, Dr Jad Sassine, Dr Alexandra Solovyova, Professor Waldemar Vollmer

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This is the final published version of an article that has been published in its final definitive form by National Academy of Sciences, 2014.

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Abstract

Bacteria surround their cytoplasmic membrane with an essential, stress-bearing peptidoglycan (PG) layer. Growing and dividing cells expand their PG layer by using membrane-anchored PG synthases, which are guided by dynamic cytoskeletal elements. In Escherichia coli, growth of the mainly single-layered PG is also regulated by outer membrane-anchored lipoproteins. The lipoprotein LpoB is required for the activation of penicillin-binding protein (PBP) 1B, which is a major, bifunctional PG synthase with glycan chain polymerizing (glycosyltransferase) and peptide cross-linking (transpeptidase) activities. Here, we report the structure of LpoB, determined by NMR spectroscopy, showing an N-terminal, 54-aa-long flexible stretch followed by a globular domain with similarity to the N-terminal domain of the prevalent periplasmic protein TolB. We have identified the interaction interface between the globular domain of LpoB and the noncatalytic UvrB domain 2 homolog domain of PBP1B and modeled the complex. Amino acid exchanges within this interface weaken the PBP1B-LpoB interaction, decrease the PBP1B stimulation in vitro, and impair its function in vivo. On the contrary, the N-terminal flexible stretch of LpoB is required to stimulate PBP1B in vivo, but is dispensable in vitro. This supports a model in which LpoB spans the periplasm to interact with PBP1B and stimulate PG synthesis.


Publication metadata

Author(s): Egan AJF, Jean NL, Koumoutsi A, Bougault CM, Biboy J, Sassine J, Solovyova AS, Breukink E, Typas A, Vollmer W, Simorre JP

Publication type: Article

Publication status: Published

Journal: Proceedings of the National Academy of Sciences of the United States of America

Year: 2014

Volume: 111

Issue: 22

Pages: 8197-8202

Print publication date: 03/06/2014

Online publication date: 12/05/2014

Acceptance date: 14/04/2014

Date deposited: 16/04/2015

ISSN (print): 0027-8424

ISSN (electronic): 1091-6490

Publisher: National Academy of Sciences

URL: http://dx.doi.org/10.1073/pnas.1400376111

DOI: 10.1073/pnas.1400376111


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Funding

Funder referenceFunder name
CNRS
Commissariat a l'Energie Atomique
Commissariat a l'Energie Atomique et aux Energies Alternatives
EMBL
European Molecular Biology Laboratory (EMBL)
Sofja Kovalevskaja award
Universite Joseph Fourier
ANR-10-INSB-05-02French Infrastructure for Integrated Structural Biology
ANR-10-LABX-49-01Grenoble Alliance for Integrated Structural Biology
BB/I020012/1Biotechnology and Biological Sciences Research Council
DIVINOCELL HEALTH-F3-2009-223431European Commission
FR3050Tres Grande Infrastructure de Recherche-Resonance Magnetique Nucleaire-Tres Haut Champ (TGIR-RMN-THC) from the Centre National de la Recherche Scientifique (CNRS)

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