Ligand-induced conformational and structural dynamics changes in Escherichia coli cyclic AMP receptor protein

Aichun Dong, Jedrzej M. Malecki, Lucy Lee, John F. Carpenter, James Lee

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Cyclic AMP receptor protein (CRP) regulates the expression of a large number of genes in E. coli. It is activated by cAMP binding, which leads to some yet undefined conformational changes. These changes do not involve significant redistribution of secondary structures. A potential mechanism of activation is a ligand-induced change in structural dynamics. Hence, the cAMP-mediated conformational and structural dynamics changes in the wild-type CRP were investigated using hydrogen-deuterium exchange and Fourier transform infrared spectroscopy. Upon cAMP binding, the two functional domains within the wild-type CRP undergo conformational and structural dynamics changes in two opposite directions. While the smaller DNA-binding domain becomes more flexible, the larger cAMP-binding domain shifts to a less dynamic conformation, evidenced by a faster and a slower amide H-D exchange, respectively. To a lesser extent, binding of cGMP, a nonfunctional analogue of cAMP, also stabilizes the cAMP-binding domain, but it fails to mimic the relaxation effect of cAMP on the DNA-binding domain. Despite changes in the conformation and structural dynamics, cAMP binding does not alter significantly the secondary structural composition of the wild-type CRP. The apparent difference between functional and nonfunctional analogues of cAMP is the ability of cAMP to effect an increase in the dynamic motions of the DNA binding domain.

Original languageEnglish (US)
Pages (from-to)6660-6667
Number of pages8
JournalBiochemistry
Volume41
Issue number21
DOIs
StatePublished - May 28 2002

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Cyclic AMP Receptor Protein
Escherichia coli Proteins
Structural dynamics
Escherichia coli
Ligands
Conformations
DNA
Deuterium
Fourier Transform Infrared Spectroscopy
Amides
Hydrogen
Genes
Chemical activation
Chemical analysis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ligand-induced conformational and structural dynamics changes in Escherichia coli cyclic AMP receptor protein. / Dong, Aichun; Malecki, Jedrzej M.; Lee, Lucy; Carpenter, John F.; Lee, James.

In: Biochemistry, Vol. 41, No. 21, 28.05.2002, p. 6660-6667.

Research output: Contribution to journalArticle

Dong, Aichun ; Malecki, Jedrzej M. ; Lee, Lucy ; Carpenter, John F. ; Lee, James. / Ligand-induced conformational and structural dynamics changes in Escherichia coli cyclic AMP receptor protein. In: Biochemistry. 2002 ; Vol. 41, No. 21. pp. 6660-6667.
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