The structural basis of cooperative regulation at an alternate genetic switch

Heather W. Pinkett; Keith E. Shearwin; Steven Stayrook; Ian B. Dodd; Tom Burr; Ann Hochschild; J. Barry Egan; Mitchell Lewis

doi:10.1016/j.molcel.2006.01.019

The structural basis of cooperative regulation at an alternate genetic switch

Heather W. Pinkett, Keith E. Shearwin, Steven Stayrook, Ian B. Dodd, Tom Burr, Ann Hochschild, J. Barry Egan, Mitchell Lewis^*

^*Corresponding author for this work

Molecular Biosciences

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

25 Scopus citations

Abstract

Bacteriophage λ is a paradigm for understanding the role of cooperativity in gene regulation. Comparison of the regulatory regions of λ and the unrelated temperate bacteriophage 186 provides insight into alternate ways to assemble functional genetic switches. The structure of the C-terminal domain of the 186 repressor, determined at 2.7 Å resolution, reveals an unusual heptamer of dimers, consistent with presented genetic studies. In addition, the structure of a cooperativity mutant of the full-length 186 repressor, identified by genetic screens, was solved to 1.95 Å resolution. These structures provide a molecular basis for understanding lysogenic regulation in 186. Whereas the overall fold of the 186 and λ repressor monomers is remarkably similar, the way the two repressors cooperatively assemble is quite different and explains in part the differences in their regulatory activity.

Original language	English (US)
Pages (from-to)	605-615
Number of pages	11
Journal	Molecular cell
Volume	21
Issue number	5
DOIs	https://doi.org/10.1016/j.molcel.2006.01.019
State	Published - Mar 3 2006

Funding

This work was supported by National Institute of Health grants to M.L., A.H., and J.B.E. and is based on research conducted at the NSLS beamlines X25 and X12B at Brookhaven National Laboratory.

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2006.01.019

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title = "The structural basis of cooperative regulation at an alternate genetic switch",

abstract = "Bacteriophage λ is a paradigm for understanding the role of cooperativity in gene regulation. Comparison of the regulatory regions of λ and the unrelated temperate bacteriophage 186 provides insight into alternate ways to assemble functional genetic switches. The structure of the C-terminal domain of the 186 repressor, determined at 2.7 {\AA} resolution, reveals an unusual heptamer of dimers, consistent with presented genetic studies. In addition, the structure of a cooperativity mutant of the full-length 186 repressor, identified by genetic screens, was solved to 1.95 {\AA} resolution. These structures provide a molecular basis for understanding lysogenic regulation in 186. Whereas the overall fold of the 186 and λ repressor monomers is remarkably similar, the way the two repressors cooperatively assemble is quite different and explains in part the differences in their regulatory activity.",

author = "Pinkett, {Heather W.} and Shearwin, {Keith E.} and Steven Stayrook and Dodd, {Ian B.} and Tom Burr and Ann Hochschild and Egan, {J. Barry} and Mitchell Lewis",

note = "Funding Information: This work was supported by National Institute of Health grants to M.L., A.H., and J.B.E. and is based on research conducted at the NSLS beamlines X25 and X12B at Brookhaven National Laboratory. ",

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AU - Stayrook, Steven

AU - Dodd, Ian B.

AU - Burr, Tom

AU - Hochschild, Ann

AU - Egan, J. Barry

AU - Lewis, Mitchell

N1 - Funding Information: This work was supported by National Institute of Health grants to M.L., A.H., and J.B.E. and is based on research conducted at the NSLS beamlines X25 and X12B at Brookhaven National Laboratory.

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Y1 - 2006/3/3

N2 - Bacteriophage λ is a paradigm for understanding the role of cooperativity in gene regulation. Comparison of the regulatory regions of λ and the unrelated temperate bacteriophage 186 provides insight into alternate ways to assemble functional genetic switches. The structure of the C-terminal domain of the 186 repressor, determined at 2.7 Å resolution, reveals an unusual heptamer of dimers, consistent with presented genetic studies. In addition, the structure of a cooperativity mutant of the full-length 186 repressor, identified by genetic screens, was solved to 1.95 Å resolution. These structures provide a molecular basis for understanding lysogenic regulation in 186. Whereas the overall fold of the 186 and λ repressor monomers is remarkably similar, the way the two repressors cooperatively assemble is quite different and explains in part the differences in their regulatory activity.

AB - Bacteriophage λ is a paradigm for understanding the role of cooperativity in gene regulation. Comparison of the regulatory regions of λ and the unrelated temperate bacteriophage 186 provides insight into alternate ways to assemble functional genetic switches. The structure of the C-terminal domain of the 186 repressor, determined at 2.7 Å resolution, reveals an unusual heptamer of dimers, consistent with presented genetic studies. In addition, the structure of a cooperativity mutant of the full-length 186 repressor, identified by genetic screens, was solved to 1.95 Å resolution. These structures provide a molecular basis for understanding lysogenic regulation in 186. Whereas the overall fold of the 186 and λ repressor monomers is remarkably similar, the way the two repressors cooperatively assemble is quite different and explains in part the differences in their regulatory activity.

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The structural basis of cooperative regulation at an alternate genetic switch

Abstract

Funding

ASJC Scopus subject areas

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