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 ?-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 ?-turn, show significant disorder, indicating that molecular dynamics simulations tend to overstabilize ideally folded ?-turn structures in NTL91-39. In addition, G24-label spectra provide evidence for a partially disordered ?-helix backbone that participates in hydrogen bonding with the surrounding water.

SUBMITTER: Baiz CR 

PROVIDER: S-EPMC4390782 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature