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Molecular-dynamics simulations of C- and N-terminal peptide derivatives of GCN4-p1 in aqueous solution.
Chem Biodivers. 2005 Aug; 2(8):1086-104.CB

Abstract

We report the investigation of two 16-residue peptides in aqueous solution by means of molecular-dynamics simulations. The peptides constitute the C- and N-terminal halves of the 33-residue monomer whose dimer constitutes the leucine zipper of the yeast transcriptional activator, denoted GCN4-p1. To examine a hypothesis about coiled-coil formation, in which the C-terminal half contains a helix-formation trigger site absent in the N-terminal half, experimental studies of the two peptides have determined their helix propensities under several conditions of temperature, pH, and salt concentration with circular dichroism. An NMR experiment provides additional evidence. At temperatures of 278 and 325 K and pH 7.5, mixtures of alpha- and pi-helical secondary structure constitute the most probable conformations in both C- and N-terminal halves. A bifurcated salt bridge between Arg25 and Glu22/20 correlates with the structural fluctuations of the C-terminal half. It also exhibits a persistent loop at the N-terminal end involving the side chains of His18 and Glu22, which is reminiscent of helix-capping boxes. Nonreversible unfolding appears to occur abruptly in the Arg25 mutant, suggesting a cooperative event. Analysis does not indicate that the N-terminal half is less stable than the C-terminal half, indicating that 100 ns is too short a period to observe complete unfolding.

Authors+Show Affiliations

Missimer JH
Biomolecular Research, Paul Scherrer Institut, CH-5232 Villigen. john.missimer@psi.ch
Steinmetz MO
No affiliation info available
Jahnke W
No affiliation info available
Winkler FK
No affiliation info available
van Gunsteren WF
No affiliation info available
Daura X
No affiliation info available

MeSH

Amino Acid SequenceBasic-Leucine Zipper Transcription FactorsComputer SimulationDNA-Binding ProteinsModels, MolecularProtein ConformationSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSolutionsTranscription Factors

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17193192

Citation

Missimer, John H., et al. "Molecular-dynamics Simulations of C- and N-terminal Peptide Derivatives of GCN4-p1 in Aqueous Solution." Chemistry & Biodiversity, vol. 2, no. 8, 2005, pp. 1086-104.
Missimer JH, Steinmetz MO, Jahnke W, et al. Molecular-dynamics simulations of C- and N-terminal peptide derivatives of GCN4-p1 in aqueous solution. Chem Biodivers. 2005;2(8):1086-104.
Missimer, J. H., Steinmetz, M. O., Jahnke, W., Winkler, F. K., van Gunsteren, W. F., & Daura, X. (2005). Molecular-dynamics simulations of C- and N-terminal peptide derivatives of GCN4-p1 in aqueous solution. Chemistry & Biodiversity, 2(8), 1086-104.
Missimer JH, et al. Molecular-dynamics Simulations of C- and N-terminal Peptide Derivatives of GCN4-p1 in Aqueous Solution. Chem Biodivers. 2005;2(8):1086-104. PubMed PMID: 17193192.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular-dynamics simulations of C- and N-terminal peptide derivatives of GCN4-p1 in aqueous solution. AU - Missimer,John H, AU - Steinmetz,Michel O, AU - Jahnke,Wolfgang, AU - Winkler,Fritz K, AU - van Gunsteren,Wilfred F, AU - Daura,Xavier, PY - 2006/12/29/pubmed PY - 2007/2/6/medline PY - 2006/12/29/entrez SP - 1086 EP - 104 JF - Chemistry & biodiversity JO - Chem Biodivers VL - 2 IS - 8 N2 - We report the investigation of two 16-residue peptides in aqueous solution by means of molecular-dynamics simulations. The peptides constitute the C- and N-terminal halves of the 33-residue monomer whose dimer constitutes the leucine zipper of the yeast transcriptional activator, denoted GCN4-p1. To examine a hypothesis about coiled-coil formation, in which the C-terminal half contains a helix-formation trigger site absent in the N-terminal half, experimental studies of the two peptides have determined their helix propensities under several conditions of temperature, pH, and salt concentration with circular dichroism. An NMR experiment provides additional evidence. At temperatures of 278 and 325 K and pH 7.5, mixtures of alpha- and pi-helical secondary structure constitute the most probable conformations in both C- and N-terminal halves. A bifurcated salt bridge between Arg25 and Glu22/20 correlates with the structural fluctuations of the C-terminal half. It also exhibits a persistent loop at the N-terminal end involving the side chains of His18 and Glu22, which is reminiscent of helix-capping boxes. Nonreversible unfolding appears to occur abruptly in the Arg25 mutant, suggesting a cooperative event. Analysis does not indicate that the N-terminal half is less stable than the C-terminal half, indicating that 100 ns is too short a period to observe complete unfolding. SN - 1612-1880 UR - https://www.unboundmedicine.com/medline/citation/17193192/Molecular_dynamics_simulations_of_C__and_N_terminal_peptide_derivatives_of_GCN4_p1_in_aqueous_solution_ L2 - https://doi.org/10.1002/cbdv.200590078 DB - PRIME DP - Unbound Medicine ER -