The lac repressor hinge helix in context: The effect of the DNA binding domain and symmetry

Danielle Seckfort; Gillian C. Lynch; B. Montgomery Pettitt

doi:10.1016/j.bbagen.2020.129538

The lac repressor hinge helix in context: The effect of the DNA binding domain and symmetry

Danielle Seckfort, Gillian C. Lynch, B. Montgomery Pettitt

Biochemistry & Molecular Biology

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

1 Scopus citations

Abstract

The Lac system of genes has been an important model system in understanding gene regulation. When the dimer lac repressor protein binds to the correct DNA sequence, the hinge region of the protein goes through a disorder to order transition. The hinge region is disordered when binding to nonoperator sequences. This region of the protein must pay a conformational entropic penalty to order when it is bound to operator DNA. Structural studies show that this region is flexible. Previous simulations showed that this region is disordered when free in solution without the DNA binding domain present. Our simulations corroborate that this region is extremely flexible in solution, but we find that the presence of the DNA binding domain proximal to the hinge helix and salt make the ordered conformation more favorable even without DNA present.

Original language	English (US)
Article number	129538
Journal	Biochimica et Biophysica Acta - General Subjects
Volume	1864
Issue number	4
DOIs	https://doi.org/10.1016/j.bbagen.2020.129538
State	Published - Apr 2020

Keywords

Disorder to order transition
Disordered proteins
LacI
MD simulations
Metadynamics
Protein
Salt stability

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

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10.1016/j.bbagen.2020.129538

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title = "The lac repressor hinge helix in context: The effect of the DNA binding domain and symmetry",

abstract = "The Lac system of genes has been an important model system in understanding gene regulation. When the dimer lac repressor protein binds to the correct DNA sequence, the hinge region of the protein goes through a disorder to order transition. The hinge region is disordered when binding to nonoperator sequences. This region of the protein must pay a conformational entropic penalty to order when it is bound to operator DNA. Structural studies show that this region is flexible. Previous simulations showed that this region is disordered when free in solution without the DNA binding domain present. Our simulations corroborate that this region is extremely flexible in solution, but we find that the presence of the DNA binding domain proximal to the hinge helix and salt make the ordered conformation more favorable even without DNA present.",

keywords = "Disorder to order transition, Disordered proteins, LacI, MD simulations, Metadynamics, Protein, Salt stability",

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AB - The Lac system of genes has been an important model system in understanding gene regulation. When the dimer lac repressor protein binds to the correct DNA sequence, the hinge region of the protein goes through a disorder to order transition. The hinge region is disordered when binding to nonoperator sequences. This region of the protein must pay a conformational entropic penalty to order when it is bound to operator DNA. Structural studies show that this region is flexible. Previous simulations showed that this region is disordered when free in solution without the DNA binding domain present. Our simulations corroborate that this region is extremely flexible in solution, but we find that the presence of the DNA binding domain proximal to the hinge helix and salt make the ordered conformation more favorable even without DNA present.

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KW - MD simulations

KW - Metadynamics

KW - Protein

KW - Salt stability

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The lac repressor hinge helix in context: The effect of the DNA binding domain and symmetry

Abstract

Keywords

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