UZH-Logo

Maintenance Infos

Solution structure and dynamics of LptE from Pseudomonas aeruginosa


Moehle, Kerstin; Kocherla, Harsha; Bacsa, Bernadett; Jurt, Simon; Zerbe, Katja; Robinson, J A; Zerbe, Oliver (2016). Solution structure and dynamics of LptE from Pseudomonas aeruginosa. Biochemistry, 55(1):2936-2943.

Abstract

LptE is an outer membrane (OM) lipoprotein found in Gram-
negative bacteria, where it forms a complex with the β-barrel lipopolysaccharide(LPS) transporter LptD. The LptD/E complex plays a key role in OM biogenesis, by
translocating newly synthesized LPS molecules from the periplasm into the external leaflet of the asymmetric OM during cell growth. The LptD/E complex in Pseudomonas aeruginosa (Pa) is a target for macrocyclic β-hairpin-shaped
peptidomimetic antibiotics, which inhibit the transport of LPS to the cell surface. So far, the three-dimensional structure of the Pa LptD/E complex and the mode of
interaction with these antibiotics are unknown. Here, we report the solution structure of a Pa LptE derivative lacking the N-terminal lipid membrane anchor,
determined by multidimensional solution nuclear magnetic resonance (NMR)spectroscopy. The structure reveals a central five-stranded β-sheet against which pack
a long C-terminal and a short N-terminal α-helix, as found in homologues of LptE from other Gram-negative bacteria. One unique feature is an extended C-terminal helix in Pa LptE, which in a model of the Pa LptD/E complex appears to be long enough to contact the periplasmic domain of LptD. Chemical shift mapping experiments suggest only weak interactions occur between LptE and the oligosaccharide chains of LPS. The NMR structure of Pa LptE will be valuable for more detailed structural studies of the LptD/E complex from P. aeruginosa.

Abstract

LptE is an outer membrane (OM) lipoprotein found in Gram-
negative bacteria, where it forms a complex with the β-barrel lipopolysaccharide(LPS) transporter LptD. The LptD/E complex plays a key role in OM biogenesis, by
translocating newly synthesized LPS molecules from the periplasm into the external leaflet of the asymmetric OM during cell growth. The LptD/E complex in Pseudomonas aeruginosa (Pa) is a target for macrocyclic β-hairpin-shaped
peptidomimetic antibiotics, which inhibit the transport of LPS to the cell surface. So far, the three-dimensional structure of the Pa LptD/E complex and the mode of
interaction with these antibiotics are unknown. Here, we report the solution structure of a Pa LptE derivative lacking the N-terminal lipid membrane anchor,
determined by multidimensional solution nuclear magnetic resonance (NMR)spectroscopy. The structure reveals a central five-stranded β-sheet against which pack
a long C-terminal and a short N-terminal α-helix, as found in homologues of LptE from other Gram-negative bacteria. One unique feature is an extended C-terminal helix in Pa LptE, which in a model of the Pa LptD/E complex appears to be long enough to contact the periplasmic domain of LptD. Chemical shift mapping experiments suggest only weak interactions occur between LptE and the oligosaccharide chains of LPS. The NMR structure of Pa LptE will be valuable for more detailed structural studies of the LptD/E complex from P. aeruginosa.

Altmetrics

Downloads

2 downloads since deposited on 31 May 2016
2 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Uncontrolled Keywords:LPS biosynthesis NMR structural biology
Language:English
Date:31 May 2016
Deposited On:31 May 2016 16:17
Last Modified:30 Jun 2016 09:57
Publisher:American Chemical Society (ACS)
ISSN:0006-2960
Funders:Swiss National Science Foundation
Publisher DOI:https://doi.org/10.1021/acs.biochem.6b00313
PubMed ID:27166502

Download

[img]
Content: Accepted Version
Language: English
Filetype: PDF - Registered users only
Size: 2MB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations