A C-helix Residue, Arg-123, Has Important Roles in Both the Active and Inactive Forms of the cAMP Receptor Protein*

By H. Youn, R. Kerby, Junseock Koh, G. Roberts. 2006

14 citations recorded by the source corpus.

The cAMP receptor protein (CRP) of Escherichia coli exists in an equilibrium between active and inactive forms, and the effector, cAMP, shifts that equilibrium to the active form, thereby allowing DNA binding. For this equilibrium shift, a C-helix repositioning around the C-helix residues Thr-127 and Ser-128 has been reported as a critical local event along with proper β4/β5 positioning. Here we show that another C-helix residue, Arg-123, has a unique role in cAMP-dependent CRP activation in two different ways. First, Arg-123 is important for proper cAMP affinity, although it is not critical for the conformational change with saturating amounts of cAMP. Second, Arg-123 is optimal for stabilizing the inactive conformation of CRP when cAMP is absent, thereby allowing a maximal range of regulation by cAMP. However, Arg-123 does not appear to be critical for a functional response to cAMP, as has been proposed previously (Berman, H. M., Ten Eyck, L. F., Goodsell, D. S., Haste, N. M., Korney, A., and Taylor, S. S. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 45–50). Based on mutagenic evidence, we also propose the basis for the stabilization of the inactive form to be through a salt interaction between Asp-68 and Arg-123.

Subfields: Endocrinology, Genetics, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Lars-Oliver Essen
2. E. Krol
3. Anke Becker
4. H. Youn
5. Yusuf Tutar
6. Junseock Koh
7. G. Roberts

In Molecular Biology

1. Junseock Koh
2. H. Youn
3. G. Roberts
4. Yusuf Tutar
5. E. Krol
6. Anke Becker

Citations in the corpus

• Structural Basis of Dual Specificity of Sinorhizobium meliloti Clr, a cAMP and cGMP Receptor Protein (2023, background): “equilibrium is shifted toward the active conformation by effector binding (18).”
• Two-State Allosteric Modeling Suggests Protein Equilibrium as an Integral Component for Cyclic AMP (cAMP) Specificity in the cAMP Receptor Protein of Escherichia coli (2008, background): “CRP variants have been found that have altered ligand specificity (1, 5, 9, 14, 19, 23, 40).”
• Dynamic Fluctuations Provide the Basis of a Conformational Switch Mechanism in Apo Cyclic AMP Receptor Protein (2013, background): “The role of R123 in stabilizing apo CRP by making salt interactions either by D68 or E72 was experimentally questioned and reported that D68-R123 is the salt-bridge responsible for the stabilization [39].”