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

doi:10.7554/eLife.62614

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

Biosciences Research Group (BRG)

University Hospitals Birmingham , Birmingham , UK.
Monash University School of Management
Singapore Eye Research Institute, Singapore National Eye Center, Duke-NUS Medical School, National University of Singapore, Singapore
Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry CV2 2DX, UK; Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV2 2DX, UK

Research output: Contribution to journal › Article › peer-review

27 Citations (SciVal)

36 Downloads (Pure)

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.

Original language	English
Article number	e62614
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/eLife.62614
Publication status	Published - 14 Dec 2020

Bibliographical note

© 2020, Bryant et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Keywords

Anti-Bacterial Agents/metabolism
Bacterial Outer Membrane Proteins/metabolism
Cell Membrane/metabolism
Cell Wall/metabolism
Escherichia coli/metabolism
Escherichia coli Proteins/metabolism
Gram-Negative Bacteria/metabolism
Lipoproteins/metabolism
Protein Transport/physiology
Virulence Factors/metabolism

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10.7554/eLife.62614Licence: CC BY 3.0

Structure of dual BON-domain protein DolP identifies phospholipid binding
© 2020, Bryant et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Final published version, 3.3 MBLicence: CC BY 3.0

Cite this

Bryant, J. A., Morris, F. C., Knowles, T. J., Maderbocus, R., Heinz, E., Boelter, G., Alodaini, D., Colyer, A., Wotherspoon, P. J., Staunton, K. A., Jeeves, M., Browning, D. F., Sevastsyanovich, Y. R., Wells, T. J., Rossiter, A. E., Bavro, V. N., Sridhar, P., Ward, D. G., Chong, Z.-S., ... Henderson, I. R. (2020). Structure of dual BON-domain protein DolP identifies phospholipid binding as a new mechanism for protein localisation. eLife, 9, Article e62614. https://doi.org/10.7554/eLife.62614

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title = "Structure of dual BON-domain protein DolP identifies phospholipid binding as a new mechanism for protein localisation",

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 = "Anti-Bacterial Agents/metabolism, Bacterial Outer Membrane Proteins/metabolism, Cell Membrane/metabolism, Cell Wall/metabolism, Escherichia coli/metabolism, Escherichia coli Proteins/metabolism, Gram-Negative Bacteria/metabolism, Lipoproteins/metabolism, Protein Transport/physiology, Virulence Factors/metabolism",

author = "Bryant, \{Jack Alfred\} and Morris, \{Faye C\} and Knowles, \{Timothy J\} and Riyaz Maderbocus and Eva Heinz and Gabriela Boelter and Dema Alodaini and Adam Colyer and Wotherspoon, \{Peter J\} and Staunton, \{Kara A\} and Mark Jeeves and Browning, \{Douglas F\} and Sevastsyanovich, \{Yanina R\} and Wells, \{Timothy J\} and Rossiter, \{Amanda E\} and Bavro, \{Vassiliy N\} and Pooja Sridhar and Ward, \{Douglas G\} and Zhi-Soon Chong and Goodall, \{Emily Ca\} and Christopher Icke and Teo, \{Alvin Ck\} and Shu-Sin Chng and Roper, \{David I\} and Trevor Lithgow and Cunningham, \{Adam F\} and Manuel Banzhaf and Michael Overduin and Henderson, \{Ian R\}",

note = "{\textcopyright} 2020, Bryant et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.",

year = "2020",

month = dec,

day = "14",

doi = "10.7554/eLife.62614",

language = "English",

volume = "9",

journal = "eLife",

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Bryant, JA, Morris, FC, Knowles, TJ, Maderbocus, R, Heinz, E, Boelter, G, Alodaini, D, Colyer, A, Wotherspoon, PJ, Staunton, KA, Jeeves, M, Browning, DF, Sevastsyanovich, YR, Wells, TJ, Rossiter, AE, Bavro, VN, Sridhar, P, Ward, DG, Chong, Z-S, Goodall, EC, Icke, C, Teo, AC, Chng, S-S, Roper, DI, Lithgow, T, Cunningham, AF, Banzhaf, M, Overduin, M & Henderson, IR 2020, 'Structure of dual BON-domain protein DolP identifies phospholipid binding as a new mechanism for protein localisation', eLife, vol. 9, e62614. https://doi.org/10.7554/eLife.62614

TY - JOUR

T1 - Structure of dual BON-domain protein DolP identifies phospholipid binding as a new mechanism for protein localisation

AU - Bryant, Jack Alfred

AU - Morris, Faye C

AU - Knowles, Timothy J

AU - Maderbocus, Riyaz

AU - Heinz, Eva

AU - Boelter, Gabriela

AU - Alodaini, Dema

AU - Colyer, Adam

AU - Wotherspoon, Peter J

AU - Staunton, Kara A

AU - Jeeves, Mark

AU - Browning, Douglas F

AU - Sevastsyanovich, Yanina R

AU - Wells, Timothy J

AU - Rossiter, Amanda E

AU - Bavro, Vassiliy N

AU - Sridhar, Pooja

AU - Ward, Douglas G

AU - Chong, Zhi-Soon

AU - Goodall, Emily Ca

AU - Icke, Christopher

AU - Teo, Alvin Ck

AU - Chng, Shu-Sin

AU - Roper, David I

AU - Lithgow, Trevor

AU - Cunningham, Adam F

AU - Banzhaf, Manuel

AU - Overduin, Michael

AU - Henderson, Ian R

N1 - © 2020, Bryant et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

PY - 2020/12/14

Y1 - 2020/12/14

N2 - 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.

AB - 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.

KW - Anti-Bacterial Agents/metabolism

KW - Bacterial Outer Membrane Proteins/metabolism

KW - Cell Membrane/metabolism

KW - Cell Wall/metabolism

KW - Escherichia coli/metabolism

KW - Escherichia coli Proteins/metabolism

KW - Gram-Negative Bacteria/metabolism

KW - Lipoproteins/metabolism

KW - Protein Transport/physiology

KW - Virulence Factors/metabolism

UR - https://elifesciences.org/articles/62614#info

U2 - 10.7554/eLife.62614

DO - 10.7554/eLife.62614

M3 - Article

C2 - 33315009

SN - 2050-084X

VL - 9

JO - eLife

JF - eLife

M1 - e62614

ER -

Structure of dual BON-domain protein DolP identifies phospholipid binding as a new mechanism for protein localisation

Abstract

Bibliographical note

Keywords

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