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Sequence-specific random coil chemical shifts of intrinsically disordered proteins

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Although intrinsically disordered proteins (IDPs) are widespread in nature and play diverse and important roles in biology, they have to date been little characterized structurally. Auspiciously, intensified efforts using NMR spectroscopy have started to uncover the breadth of their conformational landscape. In particular, polypeptide backbone chemical shifts are emerging as powerful descriptors of local dynamic deviations from the "random coil" state toward canonical types of secondary structure. These digressions, in turn, can be connected to functional or dysfunctional protein states, for example, in adaptive molecular recognition and protein aggregation. Here we describe a first inventory of IDP backbone (15)N, (1)H(N), (1)H(α), (13)C(O), (13)C(β), and (13)C(α) chemical shifts using data obtained for a set of 14 proteins of unrelated sequence and function. Singular value decomposition was used to parametrize this database of 6903 measured shifts collectively in terms of 20 amino acid-specific random coil chemical shifts and 40 sequence-dependent left- and right-neighbor correction factors, affording the ncIDP library. For natively unfolded proteins, random coil backbone chemical shifts computed from the primary sequence displayed root-mean-square deviations of 0.65, 0.14, 0.12, 0.50, 0.36, and 0.41 ppm from the experimentally measured values for the (15)N, (1)H(N), (1)H(α), (13)C(O), (13)C(β), and (13)C(α) chemical shifts, respectively. The ncIDP prediction accuracy is significantly higher than that obtained with libraries for small peptides or "coil" regions of folded proteins.
Original languageEnglish
JournalJournal of the American Chemical Society
Pages (from-to)18000-3
Number of pages4
Publication statusPublished - 2010

    Research areas

  • Databases, Protein, Protein Conformation, Protein Folding, Proteins, Sequence Analysis, Protein

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