title: Determination of the structure of symmetric coiled-coil proteins from NMR data: application of the leucine zipper proteins Jun and GCN4.
abstract: Previous attempts to determine the solution structures of homodimeric 'leucine zippers' using nuclear magnetic resonance (NMR) spectroscopy have been impeded by the complete symmetry of these coiled-coil molecules, which makes it impossible a priori to distinguish between intra- and intermonomer dipolar connectivities. Consequently, a number of ad hoc approaches have been used in an attempt to derive tertiary solution structures of these molecules from the NMR data. In this paper we present a more rigorous approach for analysing the NMR spectra of symmetric coiled-coil proteins. This analysis is based on calculations of intra- and intermonomer interproton distances in the recently determined crystal structure of the GCN4 leucine zipper [O'Shea, E.K., Klemm, J.D., Kim, P.S. and Alber, T. (1991) Science, 254, 539-543] and in symmetric coiled-coil models of the leucine zippers of GCN4 and the human oncoprotein Jun which we constructed using a dynamic simulated annealing approach. This analysis has enabled the formulation of a set of rules for interpreting the NMR spectra of symmetric coiled-coil proteins and has also led to the prediction of novel dipolar connectivities which we demonstrate in a 2-D NMR spectrum of the homodimeric Jun leucine zipper.
authors.affiliation: Department of Biochemistry, University of Sydney, NSW, Australia.
authors.forename: S I
authors.initials: SI
authors.lastname: O'Donoghue
authors.forename: F K
authors.initials: FK
authors.lastname: Junius
authors.forename: G F
authors.initials: GF
authors.lastname: King
mesh_terms: D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000737:chemistry*; D006801:Humans; D016350:Leucine Zippers; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D011494:Protein Kinases / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D010446:Peptide Fragments; D016755:Proto-Oncogene Proteins c-jun; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases