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Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8197-202. doi: 10.1073/pnas.1400376111. Epub 2014 May 12.

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

Author information

1
Centre for Bacterial Cell Biology.
2
Institut de Biologie Structurale, Université Grenoble Alpes, F-38027 Grenoble, France;Institut de Biologie Structurale, Direction des Sciences du Vivant, Commissariat à l'Energie Atomique, F-38027 Grenoble, France;Institut de Biologie Structurale, Centre National de la Recherche Scientifique, F-38027 Grenoble, France;
3
European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany; and.
4
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, United Kingdom;
5
Department of Biochemistry of Membranes, Bijvoet Center for Biomolecular Research, University of Utrecht, 3584 CH, Utrecht, The Netherlands.
6
European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany; and typas@embl.de w.vollmer@ncl.ac.uk jean-pierre.simorre@ibs.fr.
7
Centre for Bacterial Cell Biology, typas@embl.de w.vollmer@ncl.ac.uk jean-pierre.simorre@ibs.fr.
8
Institut de Biologie Structurale, Université Grenoble Alpes, F-38027 Grenoble, France;Institut de Biologie Structurale, Direction des Sciences du Vivant, Commissariat à l'Energie Atomique, F-38027 Grenoble, France;Institut de Biologie Structurale, Centre National de la Recherche Scientifique, F-38027 Grenoble, France; typas@embl.de w.vollmer@ncl.ac.uk jean-pierre.simorre@ibs.fr.

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.

PMID:
24821816
PMCID:
PMC4050580
DOI:
10.1073/pnas.1400376111
[Indexed for MEDLINE]
Free PMC Article
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