Fine-mapping the contact sites of the Escherichia coli cell division proteins FtsB and FtsL on the FtsQ protein

H.B. van den Berg van Saparoea, M. Glas, I.G. Vernooij, W. Bitter, T. den Blaauwen, S. Luirink

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Background: Interactions between the components of the divisome are crucial for cell division, but detailed knowledge is lacking. Results: In vivo photo cross-linking revealed two main contact sites of FtsB and FtsL on FtsQ. Conclusion: FtsQ contains an FtsB interaction hot spot. Significance: Our results facilitate the development of protein-protein interaction inhibitors blocking cell division. Escherichia coli cell division is effected by a large assembly of proteins called the divisome, of which a subcomplex consisting of three bitopic inner membrane proteins, FtsQ, FtsB, and FtsL, is an essential part. These three proteins, hypothesized to link cytoplasmic to periplasmic events during cell division, contain large periplasmic domains that are of major importance for function and complex formation. The essential nature of this subcomplex, its low abundance, and its multiple interactions with key divisome components in the relatively accessible periplasm make it an attractive target for the development of protein-protein interaction inhibitors. Although the crystal structure of the periplasmic domain of FtsQ has been solved, the structure of the FtsQBL complex is unknown, with only very crude indications of the interactions in this complex. In this study, we used in vivo site-specific photo cross-linking to probe the surface of the FtsQ periplasmic domain for its interaction interfaces with FtsB and FtsL. An interaction hot spot for FtsB was identified around residue Ser-250 in the C-terminal region of FtsQ and a membrane-proximal interaction region for both proteins around residue Lys-59. Sequence alignment revealed a consensus motif overlapping with the C-terminal interaction hot spot, underlining the importance of this region in FtsQ. The identification of contact sites in the FtsQBL complex will guide future development of interaction inhibitors that block cell division. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Article number34
Pages (from-to)24340-24350
JournalJournal of Biological Chemistry
Issue number288
DOIs
Publication statusPublished - 2013

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Cell Division
Escherichia coli
Cells
Proteins
Periplasm
Sequence Alignment
Membrane Proteins
Crystal structure
Membranes

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@article{7113cdcd88b346d4a2cbd952a76b2bac,
title = "Fine-mapping the contact sites of the Escherichia coli cell division proteins FtsB and FtsL on the FtsQ protein",
abstract = "Background: Interactions between the components of the divisome are crucial for cell division, but detailed knowledge is lacking. Results: In vivo photo cross-linking revealed two main contact sites of FtsB and FtsL on FtsQ. Conclusion: FtsQ contains an FtsB interaction hot spot. Significance: Our results facilitate the development of protein-protein interaction inhibitors blocking cell division. Escherichia coli cell division is effected by a large assembly of proteins called the divisome, of which a subcomplex consisting of three bitopic inner membrane proteins, FtsQ, FtsB, and FtsL, is an essential part. These three proteins, hypothesized to link cytoplasmic to periplasmic events during cell division, contain large periplasmic domains that are of major importance for function and complex formation. The essential nature of this subcomplex, its low abundance, and its multiple interactions with key divisome components in the relatively accessible periplasm make it an attractive target for the development of protein-protein interaction inhibitors. Although the crystal structure of the periplasmic domain of FtsQ has been solved, the structure of the FtsQBL complex is unknown, with only very crude indications of the interactions in this complex. In this study, we used in vivo site-specific photo cross-linking to probe the surface of the FtsQ periplasmic domain for its interaction interfaces with FtsB and FtsL. An interaction hot spot for FtsB was identified around residue Ser-250 in the C-terminal region of FtsQ and a membrane-proximal interaction region for both proteins around residue Lys-59. Sequence alignment revealed a consensus motif overlapping with the C-terminal interaction hot spot, underlining the importance of this region in FtsQ. The identification of contact sites in the FtsQBL complex will guide future development of interaction inhibitors that block cell division. {\circledC} 2013 by The American Society for Biochemistry and Molecular Biology, Inc.",
author = "{van den Berg van Saparoea}, H.B. and M. Glas and I.G. Vernooij and W. Bitter and {den Blaauwen}, T. and S. Luirink",
year = "2013",
doi = "10.1074/jbc.M113.485888",
language = "English",
pages = "24340--24350",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "288",

}

Fine-mapping the contact sites of the Escherichia coli cell division proteins FtsB and FtsL on the FtsQ protein. / van den Berg van Saparoea, H.B.; Glas, M.; Vernooij, I.G.; Bitter, W.; den Blaauwen, T.; Luirink, S.

In: Journal of Biological Chemistry, No. 288, 34, 2013, p. 24340-24350.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Fine-mapping the contact sites of the Escherichia coli cell division proteins FtsB and FtsL on the FtsQ protein

AU - van den Berg van Saparoea, H.B.

AU - Glas, M.

AU - Vernooij, I.G.

AU - Bitter, W.

AU - den Blaauwen, T.

AU - Luirink, S.

PY - 2013

Y1 - 2013

N2 - Background: Interactions between the components of the divisome are crucial for cell division, but detailed knowledge is lacking. Results: In vivo photo cross-linking revealed two main contact sites of FtsB and FtsL on FtsQ. Conclusion: FtsQ contains an FtsB interaction hot spot. Significance: Our results facilitate the development of protein-protein interaction inhibitors blocking cell division. Escherichia coli cell division is effected by a large assembly of proteins called the divisome, of which a subcomplex consisting of three bitopic inner membrane proteins, FtsQ, FtsB, and FtsL, is an essential part. These three proteins, hypothesized to link cytoplasmic to periplasmic events during cell division, contain large periplasmic domains that are of major importance for function and complex formation. The essential nature of this subcomplex, its low abundance, and its multiple interactions with key divisome components in the relatively accessible periplasm make it an attractive target for the development of protein-protein interaction inhibitors. Although the crystal structure of the periplasmic domain of FtsQ has been solved, the structure of the FtsQBL complex is unknown, with only very crude indications of the interactions in this complex. In this study, we used in vivo site-specific photo cross-linking to probe the surface of the FtsQ periplasmic domain for its interaction interfaces with FtsB and FtsL. An interaction hot spot for FtsB was identified around residue Ser-250 in the C-terminal region of FtsQ and a membrane-proximal interaction region for both proteins around residue Lys-59. Sequence alignment revealed a consensus motif overlapping with the C-terminal interaction hot spot, underlining the importance of this region in FtsQ. The identification of contact sites in the FtsQBL complex will guide future development of interaction inhibitors that block cell division. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

AB - Background: Interactions between the components of the divisome are crucial for cell division, but detailed knowledge is lacking. Results: In vivo photo cross-linking revealed two main contact sites of FtsB and FtsL on FtsQ. Conclusion: FtsQ contains an FtsB interaction hot spot. Significance: Our results facilitate the development of protein-protein interaction inhibitors blocking cell division. Escherichia coli cell division is effected by a large assembly of proteins called the divisome, of which a subcomplex consisting of three bitopic inner membrane proteins, FtsQ, FtsB, and FtsL, is an essential part. These three proteins, hypothesized to link cytoplasmic to periplasmic events during cell division, contain large periplasmic domains that are of major importance for function and complex formation. The essential nature of this subcomplex, its low abundance, and its multiple interactions with key divisome components in the relatively accessible periplasm make it an attractive target for the development of protein-protein interaction inhibitors. Although the crystal structure of the periplasmic domain of FtsQ has been solved, the structure of the FtsQBL complex is unknown, with only very crude indications of the interactions in this complex. In this study, we used in vivo site-specific photo cross-linking to probe the surface of the FtsQ periplasmic domain for its interaction interfaces with FtsB and FtsL. An interaction hot spot for FtsB was identified around residue Ser-250 in the C-terminal region of FtsQ and a membrane-proximal interaction region for both proteins around residue Lys-59. Sequence alignment revealed a consensus motif overlapping with the C-terminal interaction hot spot, underlining the importance of this region in FtsQ. The identification of contact sites in the FtsQBL complex will guide future development of interaction inhibitors that block cell division. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

U2 - 10.1074/jbc.M113.485888

DO - 10.1074/jbc.M113.485888

M3 - Article

SP - 24340

EP - 24350

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 288

M1 - 34

ER -