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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



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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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


DOI: 10.1073/pnas.1400376111


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Funder referenceFunder name
Commissariat a l'Energie Atomique
Commissariat a l'Energie Atomique et aux Energies Alternatives
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
DIVINOCELL HEALTH-F3-2009-223431European Commission
BB/I020012/1Biotechnology and Biological Sciences Research Council
FR3050Tres Grande Infrastructure de Recherche-Resonance Magnetique Nucleaire-Tres Haut Champ (TGIR-RMN-THC) from the Centre National de la Recherche Scientifique (CNRS)