title: Simulations of CRP:(cAMP)2 in noncrystalline environments show a subunit transition from the open to the closed conformation.
abstract: The CRP:cAMP complex functions as a transcription factor that facilitates RNA polymerase recognition of several bacterial promoters. Detailed crystal structure information is available for CRP:(cAMP)2 and for CRP:(cAMP)2 complexed with DNA. In the crystalline environment, CRP:(cAMP)2 subunits are asymmetrically related; one subunit has a closed conformation and the other has an open conformation. The CRP:(cAMP)2 complexed with DNA shows both subunits in a closed conformation. We have studied the molecular dynamics of CRP:(cAMP)2 in noncrystalline environments. CRP:(cAMP)2 was simulated for 625 ps in vacuo and for 140 ps in solution. The crystal structure of CRP:(cAMP)2 in the absence of DNA was used as the initial conformation. Molecule optimal dynamic coordinates (MODCs) (García A, 1992, Phys Rev Lett 68:2696) were used to analyze protein conformations sampled during the course of the simulations. Two MODCs define a transition of the open subunit to a closed subunit conformation during the first 125 ps of simulation in vacuo; the resulting subunit conformation is similar to that observed in CRP:(cAMP)2:DNA crystals. Simulation of CRP:(cAMP)2 in solution showed that a transition from the open to the closed state also occurs when water is explicitly included in the calculations. These calculations suggest that the asymmetric conformation of CRP:(cAMP)2 is stabilized by crystal lattice interactions. The predicted solution conformation is more symmetric, with both subunits in a closed conformation.
authors.affiliation: Theoretical Biology and Biophysics, Los Alamos National Laboratory, New Mexico 87545, USA. angel@agua.lanl.gov
authors.forename: A E
authors.initials: AE
authors.lastname: García
authors.forename: J G
authors.initials: JG
authors.lastname: Harman
mesh_terms: D000249:Adenosine Monophosphate / Q000737:chemistry; D002373:Cyclic AMP Receptor Protein / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D002373:Cyclic AMP Receptor Protein; D000249:Adenosine Monophosphate; D004247:DNA