title: Structural disorder of folded proteins: isotope-edited 2D IR spectroscopy and Markov state modeling.
abstract: The conformational heterogeneity of the N-terminal domain of the ribosomal protein L9 (NTL91-39) in its folded state is investigated using isotope-edited two-dimensional infrared spectroscopy. Backbone carbonyls are isotope-labeled ((13)C=(18)O) at five selected positions (V3, V9, V9G13, G16, and G24) to provide a set of localized spectroscopic probes of the structure and solvent exposure at these positions. Structural interpretation of the amide I line shapes is enabled by spectral simulations carried out on structures extracted from a recent Markov state model. The V3 label spectrum indicates that the β-sheet contacts between strands I and II are well folded with minimal disorder. The V9 and V9G13 label spectra, which directly probe the hydrogen-bond contacts across the β-turn, show significant disorder, indicating that molecular dynamics simulations tend to overstabilize ideally folded β-turn structures in NTL91-39. In addition, G24-label spectra provide evidence for a partially disordered α-helix backbone that participates in hydrogen bonding with the surrounding water.
authors: Department of Chemistry, James Franck Institute and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois.
authors: Carlos R
authors: CR
authors: Baiz
authors: Department of Chemistry, James Franck Institute and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois. Electronic address: tokmakoff@uchicago.edu.
authors: Andrei
authors: A
authors: Tokmakoff
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012269:Ribosomal Proteins / Q000737:chemistry*
chemical_list: D012269:Ribosomal Proteins; C049650:ribosomal protein L9