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Structural insights into cardiolipin transfer from the Inner membrane to the outer membrane by PbgA in Gram-negative bacteria

Abstract:
The outer membrane (OM) of Gram-negative bacteria is a unique asymmetric lipid bilayer in which the outer leaflet is composed of lipopolysaccharide (LPS) and the inner leaflet is formed by glycerophospholipid (GPL). The OM plays a fundamental role in protecting Gram-negative bacteria from harsh environments and toxic compounds. The transport and assembly pathways for phospholipids of bacterial OM are unknown. Cardiolipin (CL) plays an important role in OM biogenesis and pathogenesis, and the inner membrane (IM) protein PbgA, containing five transmembrane domains and a globular domain in periplasm has been recently identified as a CL transporter from the IM to the OM with an unknown mechanism. Here we present the first two crystal structures of soluble periplasmic globular domain of PbgA from S. typhimurium and E. coli, which revealed that the globular domains of PbgA resemble the structures of the arylsulfatase protein family and contains a novel core hydrophobic pocket that may be responsible for binding and transporting CLs. Our structural and functional studies shed an important light on the mechanism of CL transport in Gram-negative bacteria from the IM to the OM, which offers great potential for the development of novel antibiotics against multi-drug resistant bacterial infections.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/srep30815

Authors


More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM
Sub department:
Structural Genomics Consortium
Department:
Unknown
Role:
Author


Publisher:
Nature Publishing Group
Journal:
Scientific Reports More from this journal
Volume:
6
Issue:
1
Pages:
30815
Publication date:
2016-08-04
Acceptance date:
2016-07-08
DOI:
EISSN:
2045-2322
ISSN:
2045-2322
Pmid:
27487745


Language:
English
Keywords:
Pubs id:
pubs:638307
UUID:
uuid:88e33dd3-70a1-45b7-8add-f5eda6251b7e
Local pid:
pubs:638307
Source identifiers:
638307
Deposit date:
2018-12-06

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