eLife (Dec 2020)
Structure of dual BON-domain protein DolP identifies phospholipid binding as a new mechanism for protein localisation
- Jack Alfred Bryant,
- Faye C Morris,
- Timothy J Knowles,
- Riyaz Maderbocus,
- Eva Heinz,
- Gabriela Boelter,
- Dema Alodaini,
- Adam Colyer,
- Peter J Wotherspoon,
- Kara A Staunton,
- Mark Jeeves,
- Douglas F Browning,
- Yanina R Sevastsyanovich,
- Timothy J Wells,
- Amanda E Rossiter,
- Vassiliy N Bavro,
- Pooja Sridhar,
- Douglas G Ward,
- Zhi-Soon Chong,
- Emily CA Goodall,
- Christopher Icke,
- Alvin CK Teo,
- Shu-Sin Chng,
- David I Roper,
- Trevor Lithgow,
- Adam F Cunningham,
- Manuel Banzhaf,
- Michael Overduin,
- Ian R Henderson
Affiliations
- Jack Alfred Bryant
- ORCiD
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Faye C Morris
- ORCiD
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Timothy J Knowles
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom; School of Biosciences, University of Birmingham, Edgbaston, United Kingdom
- Riyaz Maderbocus
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom; Institute for Cancer and Genomic Sciences, University of Birmingham, Edgbaston, United Kingdom
- Eva Heinz
- ORCiD
- Infection & Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Australia
- Gabriela Boelter
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Dema Alodaini
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Adam Colyer
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Peter J Wotherspoon
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Kara A Staunton
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Mark Jeeves
- Institute for Cancer and Genomic Sciences, University of Birmingham, Edgbaston, United Kingdom
- Douglas F Browning
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Yanina R Sevastsyanovich
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Timothy J Wells
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Amanda E Rossiter
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Vassiliy N Bavro
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Pooja Sridhar
- School of Biosciences, University of Birmingham, Edgbaston, United Kingdom
- Douglas G Ward
- School of Biosciences, University of Birmingham, Edgbaston, United Kingdom
- Zhi-Soon Chong
- Department of Chemistry, National University of Singapore, Singapore, Singapore
- Emily CA Goodall
- ORCiD
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom; Institute for Molecular Bioscience, University of Queensland, St. Lucia, Australia
- Christopher Icke
- ORCiD
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom; Institute for Molecular Bioscience, University of Queensland, St. Lucia, Australia
- Alvin CK Teo
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
- Shu-Sin Chng
- ORCiD
- Department of Chemistry, National University of Singapore, Singapore, Singapore; School of Life Sciences, The University of Warwick, Coventry, United Kingdom
- David I Roper
- School of Life Sciences, The University of Warwick, Coventry, United Kingdom
- Trevor Lithgow
- Infection & Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Australia
- Adam F Cunningham
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom; Institute of Inflammation and Immunotherapy, University of Birmingham, Edgbaston, United Kingdom
- Manuel Banzhaf
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom
- Michael Overduin
- School of Biosciences, University of Birmingham, Edgbaston, United Kingdom; Department of Biochemistry, University of Alberta, Edmonton, Canada
- Ian R Henderson
- ORCiD
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, United Kingdom; Department of Chemistry, National University of Singapore, Singapore, Singapore
- DOI
- https://doi.org/10.7554/eLife.62614
- Journal volume & issue
-
Vol. 9
Abstract
The Gram-negative outer-membrane envelops the bacterium and functions as a permeability barrier against antibiotics, detergents, and environmental stresses. Some virulence factors serve to maintain the integrity of the outer membrane, including DolP (formerly YraP) a protein of unresolved structure and function. Here, we reveal DolP is a lipoprotein functionally conserved amongst Gram-negative bacteria and that loss of DolP increases membrane fluidity. We present the NMR solution structure for Escherichia coli DolP, which is composed of two BON domains that form an interconnected opposing pair. The C-terminal BON domain binds anionic phospholipids through an extensive membrane:protein interface. This interaction is essential for DolP function and is required for sub-cellular localisation of the protein to the cell division site, providing evidence of subcellular localisation of these phospholipids within the outer membrane. The structure of DolP provides a new target for developing therapies that disrupt the integrity of the bacterial cell envelope.
Keywords
