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

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 C A Goodall; Christopher Icke; Alvin 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 localization

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 C A GoodallChristopher Icke, Alvin Teo, Shu-Sin Chng, David I Roper, Trevor Lithgow, Adam F Cunningham, Manuel Banzhaf, Michael Overduin, Ian R Henderson

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

4 Citations (Scopus)

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 among 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 localization of the protein to the cell division site, providing evidence of subcellular localization 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
Journal	eLife
Volume	9
Early online date	14 Dec 2020
DOIs	https://doi.org/10.7554/eLife.62614
Publication status	Published - Dec 2020

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10.7554/eLife.62614

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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 localization. eLife, 9. Advance online publication. https://doi.org/10.7554/eLife.62614

@article{a93fd1c624b846ecab982c348e4cbbda,

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

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 among 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 localization of the protein to the cell division site, providing evidence of subcellular localization 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.",

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 C A} and Christopher Icke and Alvin Teo 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.",

year = "2020",

month = dec,

doi = "10.7554/eLife.62614",

language = "English",

volume = "9",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

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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, ECA, Icke, C, Teo, A, 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 localization', eLife, vol. 9. 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 localization

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 C A

AU - Icke, Christopher

AU - Teo, Alvin

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

PY - 2020/12

Y1 - 2020/12

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 among 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 localization of the protein to the cell division site, providing evidence of subcellular localization 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 among 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 localization of the protein to the cell division site, providing evidence of subcellular localization 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.

U2 - 10.7554/eLife.62614

DO - 10.7554/eLife.62614

M3 - Article

C2 - 33315009

SN - 2050-084X

VL - 9

JO - eLife

JF - eLife

ER -

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

Abstract

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